The Association of Monocyte Subtypes Frequency and Serum TNF-α and TGF-β Levels with Diabetic Wound Grade
-
Vahid Asghariazar
,
Roya Dolatkhah
,
Sepideh Moharami
,
Sohrab Iranpour
,
Amirhossein Adli
,
Majid Eterafi
,
Elham Safarzadeh
Abstract
The exact mechanisms underlying impaired wound healing in diabetes are not fully understood. In this study, we aimed to investigate the effect of classical and non-classical monocyte ratios along with TNF-α and TGF-β plasma levels on diabetic wound healing.
Twenty-four patients with confirmed type 2 diabetes and twenty healthy controls were enrolled in this study. The peripheral blood mononuclear cells (PBMC) isolation was performed by Ficoll-Paque density gradient centrifugation method. The frequency of different subsets of monocytes was characterized in diabetic patients and healthy controls using flow cytometry. TNF-α and TGF-β plasma levels were measured by the enzyme-linked immunosorbent assay (ELISA) method.
We found a significant difference in the frequency of classical and non-classical monocytes in healthy controls and diabetic patients. The plasma level of TNF-α was higher in diabetic patients than in healthy controls, and its level was associated with wound grade. Moreover, the plasma level of TGF-β was lower in diabetic patients rather than healthy controls. Also, our data showed a higher percentage of non-classical monocytes as wound grade increased.
In conclusion, the wound healing process is affected by diabetes via changes in non-classical and classical monocyte percentages, which may be the result of TNF-α increase and TGF-β levels decreasing in diabetic patients’ plasma.
1. Ong KL, Stafford LK, McLaughlin SA, et al. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. The Lancet. 2023.
2. Alwin Robert A, Abdulaziz Al Dawish M, Braham R, Ali Musallam M, Abdullah Al Hayek A, Hazza Al Kahtany N. Type 2 diabetes mellitus in Saudi Arabia: major challenges and possible solutions. Curr Diabetes Rev. 2017;13(1):59-64.
3. Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol. 2018;14(2):88-98.
4. Bashir H, Bhat SA, Majid S, et al. Role of inflammatory mediators (TNF-α, IL-6, CRP), biochemical and hematological parameters in type 2 diabetes mellitus patients of Kashmir, India. Med J Islam Repub Iran. 2020;34:5.
5. Wang X, Yuan C-X, Xu B, Yu Z. Diabetic foot ulcers: Classification, risk factors and management. World J Diabetes. 2022;13(12):1049.
6. Ousey K, Chadwick P, Jawień A, et al. Identifying and treating foot ulcers in patients with diabetes: saving feet, legs and lives. J Wound Care. 2018;27(Sup5):S1-S52.
7. Rodrigues M, Kosaric N, Bonham CA, Gurtner GC. Wound healing: a cellular perspective. Physiological Rev. 2019;99(1):665-706.
8. Wicks K, Torbica T, Mace KA. Myeloid cell dysfunction and the pathogenesis of the diabetic chronic wound. Elsevier; 2014:341-353.Cash JL, Martin P. Myeloid cells in cutaneous wound repair. Myeloid Cells in Health and Disease: A Synthesis. 2017:385-403.
9. He L, Marneros AG. Macrophages are essential for the early wound healing response and the formation of a fibrovascular scar. Am J Pathol. 2013;182(6):2407-17.
10. Fadini G, de Kreutzenberg SV, Boscaro E, et al. An unbalanced monocyte polarisation in peripheral blood and bone marrow of patients with type 2 diabetes has an impact on microangiopathy. Diabetologia. 2013;56:1856-66.
11. Wong KL, Yeap WH, Tai JJY, Ong SM, Dang TM, Wong SC. The three human monocyte subsets: implications for health and disease. Immunol Res. 2012;53:41-57.
12. Moroni F, Ammirati E, Norata GD, Magnoni M, Camici PG. The role of monocytes and macrophages in human atherosclerosis, plaque neoangiogenesis, and atherothrombosis. Med Inflamm. 2019;2019
13. Mukherjee R, Kanti Barman P, Kumar Thatoi P, Tripathy R, Kumar Das B, Ravindran B. Non-classical monocytes display inflammatory features: validation in sepsis and systemic lupus erythematous. Sci Rep. 2015;5(1):13886.
14. Ong S-M, Hadadi E, Dang T-M, et al. The pro-inflammatory phenotype of the human non-classical monocyte subset is attributed to senescence. Cell Death Dis. 2018;9(3):266.
15. Bharat A, McQuattie-Pimentel AC, Budinger GS. Non-classical monocytes in tissue injury and cancer. Oncotarget. 2017;8(63):106171.
16. Kiritsi D, Nyström A. The role of TGFβ in wound healing pathologies. Mech Ageing Dev. 2018;172:51-58.
17. Liu C, Feng X, Li Q, Wang Y, Li Q, Hua M. Adiponectin, TNF-α and inflammatory cytokines and risk of type 2 diabetes: a systematic review and meta-analysis. cytokine. 2016;86:100-109.
18. Baltzis D, Eleftheriadou I, Veves A. Pathogenesis and treatment of impaired wound healing in diabetes mellitus: new insights. Adv Ther. 2014;31:817-36.
19. Swoboda L, Held J. Impaired wound healing in diabetes. J Wound Care. 2022;31(10):882-885.
20. Min D, Nube V, Tao A, et al. Monocyte phenotype as a predictive marker for wound healing in diabetes-related foot ulcers. J Diabetes Complications. 2021;35(5):107889.
21. López Stewart G. Diagnostic criteria and classification of hyperglycaemia first detected in pregnancy: A World Health Organization Guideline. Diabetes Res Clin Pract. 2014;103(3):341-63.
22. Wildgruber M, Aschenbrenner T, Wendorff H, et al. The “Intermediate” CD14++ CD16+ monocyte subset increases in severe peripheral artery disease in humans. Sci Rep. 2016;6(1):39483.
23. Poitou C, Dalmas E, Renovato M, et al. CD14dimCD16+ and CD14+ CD16+ monocytes in obesity and during weight loss: relationships with fat mass and subclinical atherosclerosis. Arterioscler Thromb Vasc Biol. 2011;31(10):232230.
24. Costantini A, Viola N, Berretta A, et al. Age-related M1/M2 phenotype changes in circulating monocytes from healthy/unhealthy individuals. Aging (Albany NY). 2018;10(6):1268.
25. Ning D, Garg K, Mayer B, et al. Monocyte subtype expression patterns in septic patients with diabetes are distinct from patterns observed in obese patients. Front Med (Lausanne). 2023;9:1026298.
26. Valtierra-Alvarado MA, Delgado JC, Ramírez-Talavera SI, et al. Type 2 diabetes mellitus metabolic control correlates with the phenotype of human monocytes and monocyte-derived macrophages. J Diabetes Complications. 2020;34(11):107708.
27. Yunna C, Mengru H, Lei W, Weidong C. Macrophage M1/M2 polarization. Eur J Pharmacol. 2020;877:173090.
28. Louiselle AE, Niemiec SM, Zgheib C, Liechty KW. Macrophage polarization and diabetic wound healing. Trans Res. 2021;236:109-16.
1. Ong KL, Stafford LK, McLaughlin SA, et al. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. The Lancet. 2023.
2. Alwin Robert A, Abdulaziz Al Dawish M, Braham R, Ali Musallam M, Abdullah Al Hayek A, Hazza Al Kahtany N. Type 2 diabetes mellitus in Saudi Arabia: major challenges and possible solutions. Curr Diabetes Rev. 2017;13(1):59-64.
3. Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol. 2018;14(2):88-98.
4. Bashir H, Bhat SA, Majid S, et al. Role of inflammatory mediators (TNF-α, IL-6, CRP), biochemical and hematological parameters in type 2 diabetes mellitus patients of Kashmir, India. Med J Islam Repub Iran. 2020;34:5.
5. Wang X, Yuan C-X, Xu B, Yu Z. Diabetic foot ulcers: Classification, risk factors and management. World J Diabetes. 2022;13(12):1049.
6. Ousey K, Chadwick P, Jawień A, et al. Identifying and treating foot ulcers in patients with diabetes: saving feet, legs and lives. J Wound Care. 2018;27(Sup5):S1-S52.
7. Rodrigues M, Kosaric N, Bonham CA, Gurtner GC. Wound healing: a cellular perspective. Physiological Rev. 2019;99(1):665-706.
8. Wicks K, Torbica T, Mace KA. Myeloid cell dysfunction and the pathogenesis of the diabetic chronic wound. Elsevier; 2014:341-353.
9. He L, Marneros AG. Macrophages are essential for the early wound healing response and the formation of a fibrovascular scar. Am J Pathol. 2013;182(6):2407-17.
10. Fadini G, de Kreutzenberg SV, Boscaro E, et al. An unbalanced monocyte polarisation in peripheral blood and bone marrow of patients with type 2 diabetes has an impact on microangiopathy. Diabetologia. 2013;56:1856-66.
11. Wong KL, Yeap WH, Tai JJY, Ong SM, Dang TM, Wong SC. The three human monocyte subsets: implications for health and disease. Immunol Res. 2012;53:41-57.
12. Moroni F, Ammirati E, Norata GD, Magnoni M, Camici PG. The role of monocytes and macrophages in human atherosclerosis, plaque neoangiogenesis, and atherothrombosis. Med Inflamm. 2019;2019
13. Mukherjee R, Kanti Barman P, Kumar Thatoi P, Tripathy R, Kumar Das B, Ravindran B. Non-classical monocytes display inflammatory features: validation in sepsis and systemic lupus erythematous. Sci Rep. 2015;5(1):13886.
14. Ong S-M, Hadadi E, Dang T-M, et al. The pro-inflammatory phenotype of the human non-classical monocyte subset is attributed to senescence. Cell Death Dis. 2018;9(3):266.
15. Bharat A, McQuattie-Pimentel AC, Budinger GS. Non-classical monocytes in tissue injury and cancer. Oncotarget. 2017;8(63):106171.
16. Kiritsi D, Nyström A. The role of TGFβ in wound healing pathologies. Mech Ageing Dev. 2018;172:51-58.
17. Liu C, Feng X, Li Q, Wang Y, Li Q, Hua M. Adiponectin, TNF-α and inflammatory cytokines and risk of type 2 diabetes: a systematic review and meta-analysis. cytokine. 2016;86:100-109.
18. Baltzis D, Eleftheriadou I, Veves A. Pathogenesis and treatment of impaired wound healing in diabetes mellitus: new insights. Adv Ther. 2014;31:817-36.
19. Swoboda L, Held J. Impaired wound healing in diabetes. J Wound Care. 2022;31(10):882-885.
20. Min D, Nube V, Tao A, et al. Monocyte phenotype as a predictive marker for wound healing in diabetes-related foot ulcers. J Diabetes Complications. 2021;35(5):107889.
21. López Stewart G. Diagnostic criteria and classification of hyperglycaemia first detected in pregnancy: A World Health Organization Guideline. Diabetes Res Clin Pract. 2014;103(3):341-63.
22. Wildgruber M, Aschenbrenner T, Wendorff H, et al. The “Intermediate” CD14++ CD16+ monocyte subset increases in severe peripheral artery disease in humans. Sci Rep. 2016;6(1):39483.
23. Poitou C, Dalmas E, Renovato M, et al. CD14dimCD16+ and CD14+ CD16+ monocytes in obesity and during weight loss: relationships with fat mass and subclinical atherosclerosis. Arterioscler Thromb Vasc Biol. 2011;31(10):232230.
24. Costantini A, Viola N, Berretta A, et al. Age-related M1/M2 phenotype changes in circulating monocytes from healthy/unhealthy individuals. Aging (Albany NY). 2018;10(6):1268.
25. Ning D, Garg K, Mayer B, et al. Monocyte subtype expression patterns in septic patients with diabetes are distinct from patterns observed in obese patients. Front Med (Lausanne). 2023;9:1026298.
26. Valtierra-Alvarado MA, Delgado JC, Ramírez-Talavera SI, et al. Type 2 diabetes mellitus metabolic control correlates with the phenotype of human monocytes and monocyte-derived macrophages. J Diabetes Complications. 2020;34(11):107708.
27. Yunna C, Mengru H, Lei W, Weidong C. Macrophage M1/M2 polarization. Eur J Pharmacol. 2020;877:173090.
28. Louiselle AE, Niemiec SM, Zgheib C, Liechty KW. Macrophage polarization and diabetic wound healing. Trans Res. 2021;236:109-16.
29. Nirenjen S, Narayanan J, Tamilanban T, et al. Exploring the contribution of pro-inflammatory cytokines to impaired wound healing in diabetes. Frontiers in immunology. 2023;14:1216321.
30. Aikawa E, Fujita R, Asai M, Kaneda Y, Tamai K. Receptor for advanced glycation end products-mediated signaling impairs the maintenance of bone marrow mesenchymal stromal cells in diabetic model mice. Stem Cells Dev. 2016;25(22):1721-32.
31. Chu C-M, Kuo S-F, Hua C-C, Wu S-Y, Chuang D-Y, Wu H-P. Glucose increases interleukin-12 gene expression and production in stimulated peripheral blood mononuclear cells of type 2 diabetes patients. Biomed J. 2014;37(5).
32. Zhang C, Bi Y, Jin G, Gan H, Yu L. High and fluctuating glucose levels increase the expression and secretion of interleukin‑18 in mouse peritoneal macrophages. Mol Med Rep. 2015;12(2):2715-20.
33. Alves MJ, Figuerêdo RG, Azevedo FF, et al. Adipose tissue fibrosis in human cancer cachexia: the role of TGFβ pathway. BMC cancer. 2017;17:1-12.
34. Roche P, P Czubryt M. Transcriptional control of collagen I gene expression. C Cardiovasc Hematol Disord Drug Targets. 2014;14(2):107-20.
35. Siqueira MF, Li J, Chehab L, et al. Impaired wound healing in mouse models of diabetes is mediated by TNF-α dysregulation and associated with enhanced activation of forkhead box O1 (FOXO1). Diabetologia. 2010;53:378-88.
36. Behl Y, Krothapalli P, Desta T, DiPiazza A, Roy S, Graves DT. Diabetes-enhanced tumor necrosis factor-α production promotes apoptosis and the loss of retinal microvascular cells in type 1 and type 2 models of diabetic retinopathy. Am J Pathol. 2008;172(5):1411-8.
37. Zhao L, Zou Y, Liu F. Transforming growth factor-beta1 in diabetic kidney disease. Front Cell Dev Biol. 2020;8:187.
38. Juhl P, Bondesen S, Hawkins CL, et al. Dermal fibroblasts have different extracellular matrix profiles induced by TGF-β, PDGF and IL-6 in a model for skin fibrosis. Sci Rep. 2020;10(1):17300.
2. Alwin Robert A, Abdulaziz Al Dawish M, Braham R, Ali Musallam M, Abdullah Al Hayek A, Hazza Al Kahtany N. Type 2 diabetes mellitus in Saudi Arabia: major challenges and possible solutions. Curr Diabetes Rev. 2017;13(1):59-64.
3. Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol. 2018;14(2):88-98.
4. Bashir H, Bhat SA, Majid S, et al. Role of inflammatory mediators (TNF-α, IL-6, CRP), biochemical and hematological parameters in type 2 diabetes mellitus patients of Kashmir, India. Med J Islam Repub Iran. 2020;34:5.
5. Wang X, Yuan C-X, Xu B, Yu Z. Diabetic foot ulcers: Classification, risk factors and management. World J Diabetes. 2022;13(12):1049.
6. Ousey K, Chadwick P, Jawień A, et al. Identifying and treating foot ulcers in patients with diabetes: saving feet, legs and lives. J Wound Care. 2018;27(Sup5):S1-S52.
7. Rodrigues M, Kosaric N, Bonham CA, Gurtner GC. Wound healing: a cellular perspective. Physiological Rev. 2019;99(1):665-706.
8. Wicks K, Torbica T, Mace KA. Myeloid cell dysfunction and the pathogenesis of the diabetic chronic wound. Elsevier; 2014:341-353.Cash JL, Martin P. Myeloid cells in cutaneous wound repair. Myeloid Cells in Health and Disease: A Synthesis. 2017:385-403.
9. He L, Marneros AG. Macrophages are essential for the early wound healing response and the formation of a fibrovascular scar. Am J Pathol. 2013;182(6):2407-17.
10. Fadini G, de Kreutzenberg SV, Boscaro E, et al. An unbalanced monocyte polarisation in peripheral blood and bone marrow of patients with type 2 diabetes has an impact on microangiopathy. Diabetologia. 2013;56:1856-66.
11. Wong KL, Yeap WH, Tai JJY, Ong SM, Dang TM, Wong SC. The three human monocyte subsets: implications for health and disease. Immunol Res. 2012;53:41-57.
12. Moroni F, Ammirati E, Norata GD, Magnoni M, Camici PG. The role of monocytes and macrophages in human atherosclerosis, plaque neoangiogenesis, and atherothrombosis. Med Inflamm. 2019;2019
13. Mukherjee R, Kanti Barman P, Kumar Thatoi P, Tripathy R, Kumar Das B, Ravindran B. Non-classical monocytes display inflammatory features: validation in sepsis and systemic lupus erythematous. Sci Rep. 2015;5(1):13886.
14. Ong S-M, Hadadi E, Dang T-M, et al. The pro-inflammatory phenotype of the human non-classical monocyte subset is attributed to senescence. Cell Death Dis. 2018;9(3):266.
15. Bharat A, McQuattie-Pimentel AC, Budinger GS. Non-classical monocytes in tissue injury and cancer. Oncotarget. 2017;8(63):106171.
16. Kiritsi D, Nyström A. The role of TGFβ in wound healing pathologies. Mech Ageing Dev. 2018;172:51-58.
17. Liu C, Feng X, Li Q, Wang Y, Li Q, Hua M. Adiponectin, TNF-α and inflammatory cytokines and risk of type 2 diabetes: a systematic review and meta-analysis. cytokine. 2016;86:100-109.
18. Baltzis D, Eleftheriadou I, Veves A. Pathogenesis and treatment of impaired wound healing in diabetes mellitus: new insights. Adv Ther. 2014;31:817-36.
19. Swoboda L, Held J. Impaired wound healing in diabetes. J Wound Care. 2022;31(10):882-885.
20. Min D, Nube V, Tao A, et al. Monocyte phenotype as a predictive marker for wound healing in diabetes-related foot ulcers. J Diabetes Complications. 2021;35(5):107889.
21. López Stewart G. Diagnostic criteria and classification of hyperglycaemia first detected in pregnancy: A World Health Organization Guideline. Diabetes Res Clin Pract. 2014;103(3):341-63.
22. Wildgruber M, Aschenbrenner T, Wendorff H, et al. The “Intermediate” CD14++ CD16+ monocyte subset increases in severe peripheral artery disease in humans. Sci Rep. 2016;6(1):39483.
23. Poitou C, Dalmas E, Renovato M, et al. CD14dimCD16+ and CD14+ CD16+ monocytes in obesity and during weight loss: relationships with fat mass and subclinical atherosclerosis. Arterioscler Thromb Vasc Biol. 2011;31(10):232230.
24. Costantini A, Viola N, Berretta A, et al. Age-related M1/M2 phenotype changes in circulating monocytes from healthy/unhealthy individuals. Aging (Albany NY). 2018;10(6):1268.
25. Ning D, Garg K, Mayer B, et al. Monocyte subtype expression patterns in septic patients with diabetes are distinct from patterns observed in obese patients. Front Med (Lausanne). 2023;9:1026298.
26. Valtierra-Alvarado MA, Delgado JC, Ramírez-Talavera SI, et al. Type 2 diabetes mellitus metabolic control correlates with the phenotype of human monocytes and monocyte-derived macrophages. J Diabetes Complications. 2020;34(11):107708.
27. Yunna C, Mengru H, Lei W, Weidong C. Macrophage M1/M2 polarization. Eur J Pharmacol. 2020;877:173090.
28. Louiselle AE, Niemiec SM, Zgheib C, Liechty KW. Macrophage polarization and diabetic wound healing. Trans Res. 2021;236:109-16.
1. Ong KL, Stafford LK, McLaughlin SA, et al. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. The Lancet. 2023.
2. Alwin Robert A, Abdulaziz Al Dawish M, Braham R, Ali Musallam M, Abdullah Al Hayek A, Hazza Al Kahtany N. Type 2 diabetes mellitus in Saudi Arabia: major challenges and possible solutions. Curr Diabetes Rev. 2017;13(1):59-64.
3. Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol. 2018;14(2):88-98.
4. Bashir H, Bhat SA, Majid S, et al. Role of inflammatory mediators (TNF-α, IL-6, CRP), biochemical and hematological parameters in type 2 diabetes mellitus patients of Kashmir, India. Med J Islam Repub Iran. 2020;34:5.
5. Wang X, Yuan C-X, Xu B, Yu Z. Diabetic foot ulcers: Classification, risk factors and management. World J Diabetes. 2022;13(12):1049.
6. Ousey K, Chadwick P, Jawień A, et al. Identifying and treating foot ulcers in patients with diabetes: saving feet, legs and lives. J Wound Care. 2018;27(Sup5):S1-S52.
7. Rodrigues M, Kosaric N, Bonham CA, Gurtner GC. Wound healing: a cellular perspective. Physiological Rev. 2019;99(1):665-706.
8. Wicks K, Torbica T, Mace KA. Myeloid cell dysfunction and the pathogenesis of the diabetic chronic wound. Elsevier; 2014:341-353.
9. He L, Marneros AG. Macrophages are essential for the early wound healing response and the formation of a fibrovascular scar. Am J Pathol. 2013;182(6):2407-17.
10. Fadini G, de Kreutzenberg SV, Boscaro E, et al. An unbalanced monocyte polarisation in peripheral blood and bone marrow of patients with type 2 diabetes has an impact on microangiopathy. Diabetologia. 2013;56:1856-66.
11. Wong KL, Yeap WH, Tai JJY, Ong SM, Dang TM, Wong SC. The three human monocyte subsets: implications for health and disease. Immunol Res. 2012;53:41-57.
12. Moroni F, Ammirati E, Norata GD, Magnoni M, Camici PG. The role of monocytes and macrophages in human atherosclerosis, plaque neoangiogenesis, and atherothrombosis. Med Inflamm. 2019;2019
13. Mukherjee R, Kanti Barman P, Kumar Thatoi P, Tripathy R, Kumar Das B, Ravindran B. Non-classical monocytes display inflammatory features: validation in sepsis and systemic lupus erythematous. Sci Rep. 2015;5(1):13886.
14. Ong S-M, Hadadi E, Dang T-M, et al. The pro-inflammatory phenotype of the human non-classical monocyte subset is attributed to senescence. Cell Death Dis. 2018;9(3):266.
15. Bharat A, McQuattie-Pimentel AC, Budinger GS. Non-classical monocytes in tissue injury and cancer. Oncotarget. 2017;8(63):106171.
16. Kiritsi D, Nyström A. The role of TGFβ in wound healing pathologies. Mech Ageing Dev. 2018;172:51-58.
17. Liu C, Feng X, Li Q, Wang Y, Li Q, Hua M. Adiponectin, TNF-α and inflammatory cytokines and risk of type 2 diabetes: a systematic review and meta-analysis. cytokine. 2016;86:100-109.
18. Baltzis D, Eleftheriadou I, Veves A. Pathogenesis and treatment of impaired wound healing in diabetes mellitus: new insights. Adv Ther. 2014;31:817-36.
19. Swoboda L, Held J. Impaired wound healing in diabetes. J Wound Care. 2022;31(10):882-885.
20. Min D, Nube V, Tao A, et al. Monocyte phenotype as a predictive marker for wound healing in diabetes-related foot ulcers. J Diabetes Complications. 2021;35(5):107889.
21. López Stewart G. Diagnostic criteria and classification of hyperglycaemia first detected in pregnancy: A World Health Organization Guideline. Diabetes Res Clin Pract. 2014;103(3):341-63.
22. Wildgruber M, Aschenbrenner T, Wendorff H, et al. The “Intermediate” CD14++ CD16+ monocyte subset increases in severe peripheral artery disease in humans. Sci Rep. 2016;6(1):39483.
23. Poitou C, Dalmas E, Renovato M, et al. CD14dimCD16+ and CD14+ CD16+ monocytes in obesity and during weight loss: relationships with fat mass and subclinical atherosclerosis. Arterioscler Thromb Vasc Biol. 2011;31(10):232230.
24. Costantini A, Viola N, Berretta A, et al. Age-related M1/M2 phenotype changes in circulating monocytes from healthy/unhealthy individuals. Aging (Albany NY). 2018;10(6):1268.
25. Ning D, Garg K, Mayer B, et al. Monocyte subtype expression patterns in septic patients with diabetes are distinct from patterns observed in obese patients. Front Med (Lausanne). 2023;9:1026298.
26. Valtierra-Alvarado MA, Delgado JC, Ramírez-Talavera SI, et al. Type 2 diabetes mellitus metabolic control correlates with the phenotype of human monocytes and monocyte-derived macrophages. J Diabetes Complications. 2020;34(11):107708.
27. Yunna C, Mengru H, Lei W, Weidong C. Macrophage M1/M2 polarization. Eur J Pharmacol. 2020;877:173090.
28. Louiselle AE, Niemiec SM, Zgheib C, Liechty KW. Macrophage polarization and diabetic wound healing. Trans Res. 2021;236:109-16.
29. Nirenjen S, Narayanan J, Tamilanban T, et al. Exploring the contribution of pro-inflammatory cytokines to impaired wound healing in diabetes. Frontiers in immunology. 2023;14:1216321.
30. Aikawa E, Fujita R, Asai M, Kaneda Y, Tamai K. Receptor for advanced glycation end products-mediated signaling impairs the maintenance of bone marrow mesenchymal stromal cells in diabetic model mice. Stem Cells Dev. 2016;25(22):1721-32.
31. Chu C-M, Kuo S-F, Hua C-C, Wu S-Y, Chuang D-Y, Wu H-P. Glucose increases interleukin-12 gene expression and production in stimulated peripheral blood mononuclear cells of type 2 diabetes patients. Biomed J. 2014;37(5).
32. Zhang C, Bi Y, Jin G, Gan H, Yu L. High and fluctuating glucose levels increase the expression and secretion of interleukin‑18 in mouse peritoneal macrophages. Mol Med Rep. 2015;12(2):2715-20.
33. Alves MJ, Figuerêdo RG, Azevedo FF, et al. Adipose tissue fibrosis in human cancer cachexia: the role of TGFβ pathway. BMC cancer. 2017;17:1-12.
34. Roche P, P Czubryt M. Transcriptional control of collagen I gene expression. C Cardiovasc Hematol Disord Drug Targets. 2014;14(2):107-20.
35. Siqueira MF, Li J, Chehab L, et al. Impaired wound healing in mouse models of diabetes is mediated by TNF-α dysregulation and associated with enhanced activation of forkhead box O1 (FOXO1). Diabetologia. 2010;53:378-88.
36. Behl Y, Krothapalli P, Desta T, DiPiazza A, Roy S, Graves DT. Diabetes-enhanced tumor necrosis factor-α production promotes apoptosis and the loss of retinal microvascular cells in type 1 and type 2 models of diabetic retinopathy. Am J Pathol. 2008;172(5):1411-8.
37. Zhao L, Zou Y, Liu F. Transforming growth factor-beta1 in diabetic kidney disease. Front Cell Dev Biol. 2020;8:187.
38. Juhl P, Bondesen S, Hawkins CL, et al. Dermal fibroblasts have different extracellular matrix profiles induced by TGF-β, PDGF and IL-6 in a model for skin fibrosis. Sci Rep. 2020;10(1):17300.
| Files | ||
| Issue | Vol 24 No 2 (2025) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v24i2.18145 | |
| Keywords | ||
| Diabetes mellitus Inflammation Monocytes Type 2 Wound healing | ||
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How to Cite
1.
Asghariazar V, Dolatkhah R, Moharami S, Iranpour S, Adli A, Eterafi M, Safarzadeh E. The Association of Monocyte Subtypes Frequency and Serum TNF-α and TGF-β Levels with Diabetic Wound Grade. Iran J Allergy Asthma Immunol. 2025;24(2):170-179.
