Inhibition of Airway Contraction and Inflammation by Pomalidomide in a Male Wistar Rat Model of Ovalbumin-induced Asthma
,
Abstract
Asthma is a chronic inflammatory disease of the airways of the lungs. Pomalidomide (POM) a therapy for multiple myeloma has been stated to have an anti-inflammatory effect. The main goal of the present study was to assess its possible effect on airway contraction and inflammation in a rat model of ovalbumin-induced asthma. Different groups of rats received saline or pomalidomide (0.4, 0.8 mg/kg) or dexamethasone (0.6 mg/kg). The asthma was induced by ovalbumin (OVA). Trachea contraction was assayed by organ bath system. Airway histology was assessed using hematoxylin and eosin method. Serum Tumor necrosis factor alpha (TNF-α) level was analyzed by Enzyme-Linked Immunosorbent Assay and Platelet-derived growth factor (PDGFα) Gene expressions were evaluated by Real-time PCR. Pomalidomide prevented ovalbumin-induced airway contraction and histopathological damage. In addition serum, TNF-α level was significantly (p<0.05) decreased in POM treated animals compared to control (asthmatic animals that received POM vehicle). Results indicate that POM prevented the PDGF expression induced by ovalbumin. In conclusion, we found that pomalidomide ameliorated the symptoms, histopathological changes and inflammatory markers induced by ovalbumin in asthmatic rats and these effects might be related to its anti-inflammatory properties.
1. Bergeron C, Boulet LP. Structural changes in airway diseases: characteristics, Mechanisms, consequences, and pharmacologic modulation. Chest 2006; 12(9):1068–87.
2. SumitGhosh, Scott A Hoselton, Scott V Asbach, Breanne N Steffan, Steve B Wanjara, et al. B lymphocytes regulate airway granulocytic inflammation and cytokine production in a murine model of fungal allergic asthma. Cell MolImmunol 2015; 12(2):202-12.
3. GhoshS, HoseltonS, chuh J. Allergic Inflammation in Aspergillusfumigatus-Induced Fungal Asthma. Curr Allergy Asthma Rep 2015; 15(10):59.
4. Wang KCW, Le Cras TD, Larcombe AN, Zosky GR, Elliot JG, James AL, Noble PB.Independent and combined effects of airway remodelling and allergy on airway responsiveness. ClinSci (Lond) 2018; 132(3):327-38.
5. Elaidy SM1, Essawy SS2, Hussain MA3, El-Kherbetawy MK4, Hamed ER5. Modulation of the IL-23/IL-17 axis by fenofibrate ameliorates the ovalbumin/lipopolysaccharide-induced airway inflammation and bronchial asthma in rats. NaunynSchmiedebergs Arch Pharmacol 2018; 391(3):309-21.
6. Ghosh S1, Hoselton SA, Dorsam GP, Schuh JM. Eosinophils in fungus-associated allergic pulmonary disease. Front Pharmacol 2013; 4:8.
7. Ghosh S1, Hoselton SA, SchuhJM.μ-chain-deficient mice possess B-1 cells and produce IgG and IgE, but Not IgA, following systemic sensitization and inhalational challenge in a fungal asthma model. J Immunol 2012; 189(3):1322-9.
8. Wenzel SE. Phenotypes in asthma: useful guides for therapy, distinct biological processes, or both? Am J RespirCrit Care Med 2004; 1(70):579–80.
9. Kim YH, Choi YJ, Lee EJ, Kang MK, Park SH, Kim DY, Oh H, Park SJ, Kang YH. Novel glutathione-containing dry-yeast extracts inhibit eosinophilia and mucus overproduction in a murine model of asthma. Nutr Res Pract. 2017; 11(6):461-9.
10. Dennis M. Lindell, Aaron A. Berlin, Matthew A. Schaller, and Nicholas W. Lukacs. B Cell Antigen Presentation Promotes Th2 Responses and Immunopathology during Chronic Allergic Lung Disease. PLoS One 2008; 3(9):e3129.
11. Yasui K, Kobayashi N, Yamazaki T, Agematsu K, Curr. Pharm. Des 2005; 1(1):395-401.
12. Wenzel SE, Szefler SJ, Leung DY, Sloan SI, Rex MD, Martin RJ. Bronchoscopic evaluation of severe asthma. persistent inflammation associated with high dose glucocorticoids. Am J RespirCrit Care Med 1997; 15(6):737–43.
13. Antoniades HN, Bravo MA, Avila RE, et al. Plateletderived growth factor in idiopathic pulmonary fibrosis. J Clin Invest 1990; 8(6):1055-64.
14. Marinelli WA, Polunovsky VA, Harmon KR, Bitterm AN PB. Role of platelet-derived growth factor in pulmonary fibrosis. Am J Respir Cell MolBiol 1991; (5):503-4.
15. Vignaud JM, Allam M, Martinet N, et al. Presence of platelet-derived growth factor in normal and fibrotic lung is specifically associated with interstitial macrophages, while both interstitial macrophages and alveolar epithelial cells express the c-sis proto-oncogene. Am J Respir Cell Mol Bio 1991; (5):531-8.
16. Shaw RJ, Benedict SH, Clark RA, King T Jr. Pathogenesis of pulmonary fibrosis in interstitial lung disease. Alveolar macrophage PDGF (B) gene activation and upregulation by interferon gamma. Am Rev Respir Dis 1991; 14(3):167-73.
17. Taylor I, Sorooshian M , Wango A, et al. Plateletderived growth factor-P mRNA in human alveolar macrophages in vivo in asthma. EurRespir J 1994; 7(11):1966-72.
18. Brewster CE, Howarth PH, Djukanovic R, Wilson J, Holgate ST, Roche WR. Myofibroblasts and subepithelial fibrosis in bronchial asthma. Am J Respir Cell MolBiol 1990; 3(5):507-11.
19. Heard B. Hyperplasia of bronchial muscle in asthma. J Pathol 1973; 1(10):319-31.
20. Ebina M , Yaegashi H , Takahashi T, Motomiya M , Tanemura M. Distribution of smooth muscles along the bronchial tree. A morphometric study of ordinary autopsy lungs. Am Rev Respir Dis 1990; 1(41):1322-6.
21. Jeffery PK. Morphology of the airway wall in asthma and in chronic obstructive pulmonary disease. Am Rev Respir Dis 1991; 143(5 pt 1):1152-8.
22. Carroll N , Elliot J, Morton A, James A. The structure of large and small airways in nonfatal and fatal asthma. Am Rev Respir Dis 1993; 14(7):405-10.
23. Ross R. Platelet-derived growth factor. Lancet 1989; 1(8648):1179-82.
24. Heldin CH. Structural and functional studies on plateletderived growth factor. EMBO J 1992; 11(12):4251-9.
25. Muller GW, Chen R, Huang SY, Corral LG, Wong LM, Patterson RT, et al. Amino-substituted thalidomide analogs: potent inhibitors of TNF-alpha production. Bioorg Med ChemLett 1999; 9(11):1625–30.
26. Marriott JB, Muller G, Stirling D, Dalgleish AG. Immunotherapeutic and antitumour potential of thalidomide analogues. Expert OpinBiolTher 2001;1:675–82.
27. Corral LG, Haslett PA, Muller GW, Chen R, Wong LM, Ocampo CJ, et al. Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-alpha. J Immunol 1999; 16(3):380–6.
28. Payvandi F, Wu L, Haley M, Schafer PH, Zhang LH, Chen RS, et al. Immunomodulatory drugs inhibit expression of cyclooxygenase-2 from TNF-alpha, IL-1beta, and LPS-stimulated human PBMC in a partially IL-10-dependent manner. Cell Immunol 2004; 2(30):81-8.
29. Ming Jen Tsai, Chinpiao Chen, Sung-Ho Chen, Yen Ta Huang, Ted H. Chiu. J Gastroenterol 2011; 4(6):822–33.
30. Schey SA, Fields P, Bartlett JB, Clarke IA, Ashan G, Knight RD, et al. Phase I study of an immunomodulatory thalidomide analog, CC-4047, in relapsed or refractory multiple myeloma J ClinOncol 2004; 2(2):3269-76.
31. Farese JP, Fox LE, Detrisac CJ, Van Gilder JM, Roberts SL, Baldwin JM. Am J Vet Res 2004; 6(5):659–64.
32. Kobayashi H, Yagyu T, Kondo T, Kurita N, Inagaki K, Haruta S, et al. Cancer Res 2005; 6(5):10464–71.
33. Kianmeher M, Ghorani V, Boskabady MH. Animal Model of Asthma, Various Methods and Measured Parameters: A Methodological Review. Iran J Allergy Asthma Immunol 2016; 15(6):445-65.
34. Sur S, Wild JS, Choudhury BK, Sur N, Alam R, Klinman DM. J Immunol 1999; 162(10):6284–93.
35. McKay A, Leung BP, McInnes IB, Thomson NC, Liew FY. J Immunol 2004; 72(5):2903–8.
36. Lowry O H, Rosebrough N J, Farr A L and Randall R J. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193:265,
37. Nakae S, Lunderius C, Ho L H, Schafer B, Tsai M, Galli S J, J Allergy Clin Immunol 2007; 119:680-6 .
38. Asano T, Kume H, Taki F, Ito S, Hasegawa Y. Thalidomide Attenuates Airway Hyperresponsiveness and Eosinophilic Inflammation in a Murine Model of Allergic Asthma. Biol Pharm Bull 2010; 33(6):1028-32.
39. Muller GW, Corral LG, Shire MG, Wang H, Moreira A, Kaplan G, et al. Structural modifications of thalidomide produce analogs with enhanced tumor necrosis factor inhibitory activity. J Med Chem 1996; 3(9):3238–40.
40. Lee HS, Kwon H-S, Park D-E, Woo YD, Kim HY, Kim H-R, et al. Thalidomide Inhibits Alternative Activation of Macrophages In Vivo and In Vitro: A Potential Mechanism of Anti-Asthmatic Effect of Thalidomide. PLoS One 2015; 10(4):e0123094.
41. Poulter LW, Power C, Burke C. The relationship between bronchial immunopathology and hyperresponsiveness in asthma. Eur Respir J 1990; 3(7):792-9.
42. Poston RN, Chanez P, Lacoste JY, Litchfield T, Lee TH, Bousquet J. Immunohistochemical characterization of the cellular infiltration in asthmatic bronchi. Am Rev Respir Dis 1992; 14(5):918-21.
43. Xin L, Jingjing W, Weiwei C, Xiaoying M, Yaqin W, Norio N, et al. Biomedecine & pharmacotherapie 2017; 95:275-286.
2. SumitGhosh, Scott A Hoselton, Scott V Asbach, Breanne N Steffan, Steve B Wanjara, et al. B lymphocytes regulate airway granulocytic inflammation and cytokine production in a murine model of fungal allergic asthma. Cell MolImmunol 2015; 12(2):202-12.
3. GhoshS, HoseltonS, chuh J. Allergic Inflammation in Aspergillusfumigatus-Induced Fungal Asthma. Curr Allergy Asthma Rep 2015; 15(10):59.
4. Wang KCW, Le Cras TD, Larcombe AN, Zosky GR, Elliot JG, James AL, Noble PB.Independent and combined effects of airway remodelling and allergy on airway responsiveness. ClinSci (Lond) 2018; 132(3):327-38.
5. Elaidy SM1, Essawy SS2, Hussain MA3, El-Kherbetawy MK4, Hamed ER5. Modulation of the IL-23/IL-17 axis by fenofibrate ameliorates the ovalbumin/lipopolysaccharide-induced airway inflammation and bronchial asthma in rats. NaunynSchmiedebergs Arch Pharmacol 2018; 391(3):309-21.
6. Ghosh S1, Hoselton SA, Dorsam GP, Schuh JM. Eosinophils in fungus-associated allergic pulmonary disease. Front Pharmacol 2013; 4:8.
7. Ghosh S1, Hoselton SA, SchuhJM.μ-chain-deficient mice possess B-1 cells and produce IgG and IgE, but Not IgA, following systemic sensitization and inhalational challenge in a fungal asthma model. J Immunol 2012; 189(3):1322-9.
8. Wenzel SE. Phenotypes in asthma: useful guides for therapy, distinct biological processes, or both? Am J RespirCrit Care Med 2004; 1(70):579–80.
9. Kim YH, Choi YJ, Lee EJ, Kang MK, Park SH, Kim DY, Oh H, Park SJ, Kang YH. Novel glutathione-containing dry-yeast extracts inhibit eosinophilia and mucus overproduction in a murine model of asthma. Nutr Res Pract. 2017; 11(6):461-9.
10. Dennis M. Lindell, Aaron A. Berlin, Matthew A. Schaller, and Nicholas W. Lukacs. B Cell Antigen Presentation Promotes Th2 Responses and Immunopathology during Chronic Allergic Lung Disease. PLoS One 2008; 3(9):e3129.
11. Yasui K, Kobayashi N, Yamazaki T, Agematsu K, Curr. Pharm. Des 2005; 1(1):395-401.
12. Wenzel SE, Szefler SJ, Leung DY, Sloan SI, Rex MD, Martin RJ. Bronchoscopic evaluation of severe asthma. persistent inflammation associated with high dose glucocorticoids. Am J RespirCrit Care Med 1997; 15(6):737–43.
13. Antoniades HN, Bravo MA, Avila RE, et al. Plateletderived growth factor in idiopathic pulmonary fibrosis. J Clin Invest 1990; 8(6):1055-64.
14. Marinelli WA, Polunovsky VA, Harmon KR, Bitterm AN PB. Role of platelet-derived growth factor in pulmonary fibrosis. Am J Respir Cell MolBiol 1991; (5):503-4.
15. Vignaud JM, Allam M, Martinet N, et al. Presence of platelet-derived growth factor in normal and fibrotic lung is specifically associated with interstitial macrophages, while both interstitial macrophages and alveolar epithelial cells express the c-sis proto-oncogene. Am J Respir Cell Mol Bio 1991; (5):531-8.
16. Shaw RJ, Benedict SH, Clark RA, King T Jr. Pathogenesis of pulmonary fibrosis in interstitial lung disease. Alveolar macrophage PDGF (B) gene activation and upregulation by interferon gamma. Am Rev Respir Dis 1991; 14(3):167-73.
17. Taylor I, Sorooshian M , Wango A, et al. Plateletderived growth factor-P mRNA in human alveolar macrophages in vivo in asthma. EurRespir J 1994; 7(11):1966-72.
18. Brewster CE, Howarth PH, Djukanovic R, Wilson J, Holgate ST, Roche WR. Myofibroblasts and subepithelial fibrosis in bronchial asthma. Am J Respir Cell MolBiol 1990; 3(5):507-11.
19. Heard B. Hyperplasia of bronchial muscle in asthma. J Pathol 1973; 1(10):319-31.
20. Ebina M , Yaegashi H , Takahashi T, Motomiya M , Tanemura M. Distribution of smooth muscles along the bronchial tree. A morphometric study of ordinary autopsy lungs. Am Rev Respir Dis 1990; 1(41):1322-6.
21. Jeffery PK. Morphology of the airway wall in asthma and in chronic obstructive pulmonary disease. Am Rev Respir Dis 1991; 143(5 pt 1):1152-8.
22. Carroll N , Elliot J, Morton A, James A. The structure of large and small airways in nonfatal and fatal asthma. Am Rev Respir Dis 1993; 14(7):405-10.
23. Ross R. Platelet-derived growth factor. Lancet 1989; 1(8648):1179-82.
24. Heldin CH. Structural and functional studies on plateletderived growth factor. EMBO J 1992; 11(12):4251-9.
25. Muller GW, Chen R, Huang SY, Corral LG, Wong LM, Patterson RT, et al. Amino-substituted thalidomide analogs: potent inhibitors of TNF-alpha production. Bioorg Med ChemLett 1999; 9(11):1625–30.
26. Marriott JB, Muller G, Stirling D, Dalgleish AG. Immunotherapeutic and antitumour potential of thalidomide analogues. Expert OpinBiolTher 2001;1:675–82.
27. Corral LG, Haslett PA, Muller GW, Chen R, Wong LM, Ocampo CJ, et al. Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-alpha. J Immunol 1999; 16(3):380–6.
28. Payvandi F, Wu L, Haley M, Schafer PH, Zhang LH, Chen RS, et al. Immunomodulatory drugs inhibit expression of cyclooxygenase-2 from TNF-alpha, IL-1beta, and LPS-stimulated human PBMC in a partially IL-10-dependent manner. Cell Immunol 2004; 2(30):81-8.
29. Ming Jen Tsai, Chinpiao Chen, Sung-Ho Chen, Yen Ta Huang, Ted H. Chiu. J Gastroenterol 2011; 4(6):822–33.
30. Schey SA, Fields P, Bartlett JB, Clarke IA, Ashan G, Knight RD, et al. Phase I study of an immunomodulatory thalidomide analog, CC-4047, in relapsed or refractory multiple myeloma J ClinOncol 2004; 2(2):3269-76.
31. Farese JP, Fox LE, Detrisac CJ, Van Gilder JM, Roberts SL, Baldwin JM. Am J Vet Res 2004; 6(5):659–64.
32. Kobayashi H, Yagyu T, Kondo T, Kurita N, Inagaki K, Haruta S, et al. Cancer Res 2005; 6(5):10464–71.
33. Kianmeher M, Ghorani V, Boskabady MH. Animal Model of Asthma, Various Methods and Measured Parameters: A Methodological Review. Iran J Allergy Asthma Immunol 2016; 15(6):445-65.
34. Sur S, Wild JS, Choudhury BK, Sur N, Alam R, Klinman DM. J Immunol 1999; 162(10):6284–93.
35. McKay A, Leung BP, McInnes IB, Thomson NC, Liew FY. J Immunol 2004; 72(5):2903–8.
36. Lowry O H, Rosebrough N J, Farr A L and Randall R J. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193:265,
37. Nakae S, Lunderius C, Ho L H, Schafer B, Tsai M, Galli S J, J Allergy Clin Immunol 2007; 119:680-6 .
38. Asano T, Kume H, Taki F, Ito S, Hasegawa Y. Thalidomide Attenuates Airway Hyperresponsiveness and Eosinophilic Inflammation in a Murine Model of Allergic Asthma. Biol Pharm Bull 2010; 33(6):1028-32.
39. Muller GW, Corral LG, Shire MG, Wang H, Moreira A, Kaplan G, et al. Structural modifications of thalidomide produce analogs with enhanced tumor necrosis factor inhibitory activity. J Med Chem 1996; 3(9):3238–40.
40. Lee HS, Kwon H-S, Park D-E, Woo YD, Kim HY, Kim H-R, et al. Thalidomide Inhibits Alternative Activation of Macrophages In Vivo and In Vitro: A Potential Mechanism of Anti-Asthmatic Effect of Thalidomide. PLoS One 2015; 10(4):e0123094.
41. Poulter LW, Power C, Burke C. The relationship between bronchial immunopathology and hyperresponsiveness in asthma. Eur Respir J 1990; 3(7):792-9.
42. Poston RN, Chanez P, Lacoste JY, Litchfield T, Lee TH, Bousquet J. Immunohistochemical characterization of the cellular infiltration in asthmatic bronchi. Am Rev Respir Dis 1992; 14(5):918-21.
43. Xin L, Jingjing W, Weiwei C, Xiaoying M, Yaqin W, Norio N, et al. Biomedecine & pharmacotherapie 2017; 95:275-286.
| Files | ||
| Issue | Vol 18, No 2 (2019) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v18i2.924 | |
| Keywords | ||
| Asthma Inflammation Platelet-derived growth factor Pomalidomide TNF- α | ||
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How to Cite
1.
Ghaderi M, Oryan S, Yousofvand N, Eidi A. Inhibition of Airway Contraction and Inflammation by Pomalidomide in a Male Wistar Rat Model of Ovalbumin-induced Asthma. Iran J Allergy Asthma Immunol. 2019;18(2):209-217.
