Effect of maresin-1 on lung inflammation and MAPK signaling pathway in asthmatic mice_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

OU Guochun ,  CHEN Xiaoju , CHEN Yong , ZENG Di , HUANG Yuewei , LIU Qin

Department of Respiratory Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P. R. China;

Corresponding author：

CHEN Xiaoju, Email: cxj9592@163.com

Keywords：

Maresin-1; Asthma; Ovalbumin; MAPK signaling pathway

DOI：

10.7507/1671-6205.201906073

Video：

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Objective To investigate the effect of maresin-1 (MaR1) on lung inflammation and MAPK signaling pathway in asthmatic mice.Methods Twenty-four female BALB/c mice were randomly divided into normal group, asthma model group, MaR1 group and dexamethasone group. The asthma model was successfully established by using ovalbumin (OVA) combined with aluminum hydroxide, and then MaR1 and dexamethasone were respectively given to asthmatic mice. Serum, bronchoalveolar lavage fluid (BALF) and lung tissue were collected for further analysis. Pathological changes of lung tissue in mice were detected by hematoxylin-eosin and periodic acid-Schiﬀ. Proportion of inflammatory cells in BALF classified by Swiss-Giemsa staining. Th2-related inflammatory cytokines, interleukin (IL)-4, IL-5, IL-13 and IgE in serum and BALF were detected by enzyme linked immunosorbent assay. The protein concentration of p-p38 and p-JNK in lung tissues were detected by Western blot.Results Compared with the normal group, the asthma model group had increased both airway inflammation and the number of goblet cells significantly (P<0.05). The number of various inflammatory cells in BALF had also increased significantly (P<0.05). The levels of IL-4, IL-5 and IL-13 in BALF and IgE and OVA-specific-IgE in serum were significantly increased (P<0.05). The protein contents of p-p38 and p-JNK in lung tissues were significantly increased (P<0.05). Compared with the asthma model group, both MaR1 and dexamethasone group had reduced inflammation and mucus secretion in lung tissue, number of inflammatory cells in BALF (P<0.05), levels of related inflammatory cytokines in BALF and IgE in serum (P<0.05), and expression of p-p38 and p-JNK proteins in lung tissue (P<0.05).Conclusions MaR1 can inhibit the production and release of both Th2-related inflammatory cytokines and IgE, effectively reduce the inflammatory response and mucus production in lung tissues of asthmatic mice, with similar effect to dexamethasone. The mechanism may be related to the down-regulation of MAPKs signaling pathway.

Citation： OU Guochun, CHEN Xiaoju, CHEN Yong, ZENG Di, HUANG Yuewei, LIU Qin. Effect of maresin-1 on lung inflammation and MAPK signaling pathway in asthmatic mice. Chinese Journal of Respiratory and Critical Care Medicine, 2020, 19(3): 234-239. doi: 10.7507/1671-6205.201906073 Copy

1.	Jehangir A, Shahzad M, Shahid K, et al. Zinc and iron complexes of oleanolic acid, (OA) attenuate allergic airway inflammation in rats. Inflammopharmacology, 2019, 27(6): 1179-1192.
2.	Zhu T, Chen Z, Chen G, et al. Curcumin attenuates asthmatic airway inflammation and mucus hypersecretion involving a PPARgamma-dependent NF-kappaB signaling pathway in vivo and in vitro. Mediators Inflamm, 2019, 2019: 4927430.
3.	Barnes PJ. Glucocorticosteroids: current and future directions. Br J Pharmacol, 2011, 163(1): 29-43.
4.	Tang S, Wan M, Huang W, et al. Maresins: Specialized proresolving lipid mediators and their potential role in inflammatory-related diseases. Mediators Inflamm, 2018, 2018: 2380319.
5.	Qiu Y, Wu Y, Zhao H, et al. Maresin 1 mitigates renal ischemia/reperfusion injury in mice via inhibition of the TLR4/MAPK/NF-kappaB pathways and activation of the Nrf2 pathway. Drug Des Devel Ther, 2019, 13: 739-745.
6.	Jin SW, Chen HJ, Li YS, et al. Maresin 1 improves the Treg/Th17 imbalance in rheumatoid arthritis through miR-21. Ann Rheum Dis, 2018, 77(11): 1644-1652.
7.	Wang H, Shi P, Huang C, et al. Maresin 1 ameliorates iron-deficient anemia in IL-10(-/-) mice with spontaneous colitis by the inhibition of hepcidin expression though the IL-6/STAT3 pathway. Am J Transl Res, 2016, 8(6): 2758-2766.
8.	Gong J, Wu ZY, Qi H, et al. Maresin 1 mitigates LPS-induced acute lung injury in mice. Br J Pharmacol, 2014, 171(14): 3539-3550.
9.	Liu X, Shen JW, Fan DP, et al. Yupingfeng San inhibits NLRP3 inflammasome to attenuate the inflammatory response in asthma mice. Front Pharmacol, 2017, 8: 944.
10.	Pu Y, Liu YQ, Liao SP, et al. Azithromycin ameliorates OVA-induced airway remodeling in Balb/c mice via suppression of epithelial-to-mesenchymal transition. Int Immunopharmacol, 2018, 58: 87-93.
11.	Fahy JV. Type 2 inflammation in asthma--present in most, absent in many. Nat Rev Immunol, 2015, 15(1): 57-65.
12.	Kuhl K, Hanania NA. Targeting IgE in asthma. Curr Opin Pulm Med, 2012, 18(1): 1-5.
13.	Krishnamoorthy N, Burkett PR, Dalli J, et al. Cutting edge: maresin-1 engages regulatory T cells to limit type 2 innate lymphoid cell activation and promote resolution of lung inflammation. J Immunol, 2015, 194(3): 863-867.
14.	Zhang Q, Wang LR, Chen BH, et al. Propofol inhibits NF-kappaB activation to ameliorate airway inflammation in ovalbumin (OVA)-induced allergic asthma mice. Int Immunopharmacol, 2017, 51: 158-164.
15.	Shin IS, Jeon WY, Shin HK, et al. Effects of montelukast on subepithelial/peribronchial fibrosis in a murine model of ovalbumin induced chronic asthma. Int Immunopharmacol, 2013, 17(3): 867-873.
16.	Cargnello M, Roux PP. Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev, 2011, 75(1): 50-83.
17.	Yin CY, Bai QF, Feng JX. MiR-216a-5p protects 16HBE cells from H₂O₂-induced oxidative stress through targeting HMGB1/NF-kB pathway. Biochem Biophys Res Commun, 2019, 508(2): 416-420.
18.	Goh FY, Upton N, Guan S, et al. Fisetin, a bioactive flavonol, attenuates allergic airway inflammation through negative regulation of NF-kappaB. Eur J Pharmacol, 2012, 679(1-3): 109-116.
19.	Goplen N, Karim Z, Guo L, et al. ERK1 is important for Th2 differentiation and development of experimental asthma. FASEB J, 2012, 26(5): 1934-1945.
20.	Schieven GL. The biology of p38 kinase: a central role in inflammation. Curr Top Med Chem, 2005, 5(10): 921-928.
21.	Zhang LL, Chen B, Fan XY, et al. LPS cooperates with poly-L-arginine to promote IL-6 and IL-8 release via the JNK signaling pathway in NCI-H292 cells. J Immunol Res, 2016, 2016: 3421060.
22.	Wang X, Tanino Y, Sato S, et al. Secretoglobin 3A2 attenuates lipopolysaccharide-induced inflammation through inhibition of ERK and JNK pathways in bronchial epithelial cells. Inflammation, 2015, 38(2): 828-834.
23.	Lee WH, Yoo HY, Kim JA, et al. Barrier protective effects of piperlonguminine in LPS-induced inflammation in vitro and in vivo. Food Chem Toxicol, 2013, 58: 149-157.
24.	Li J, Kartha S, Iasvovskaia S, et al. Regulation of human airway epithelial cell IL-8 expression by MAP kinases. Am J Physiol Lung Cell Mol Physiol, 2002, 283(4): L690-L699.
25.	Wang H, Wu Y, Ojcius DM, et al. Leptospiral hemolysins induce proinflammatory cytokines through Toll-like receptor 2-and 4-mediated JNK and NF-kappaB signaling pathways. PLoS One, 2012, 7(8): e42266.

1. Jehangir A, Shahzad M, Shahid K, et al. Zinc and iron complexes of oleanolic acid, (OA) attenuate allergic airway inflammation in rats. Inflammopharmacology, 2019, 27(6): 1179-1192.
2. Zhu T, Chen Z, Chen G, et al. Curcumin attenuates asthmatic airway inflammation and mucus hypersecretion involving a PPARgamma-dependent NF-kappaB signaling pathway in vivo and in vitro. Mediators Inflamm, 2019, 2019: 4927430.
3. Barnes PJ. Glucocorticosteroids: current and future directions. Br J Pharmacol, 2011, 163(1): 29-43.
4. Tang S, Wan M, Huang W, et al. Maresins: Specialized proresolving lipid mediators and their potential role in inflammatory-related diseases. Mediators Inflamm, 2018, 2018: 2380319.
5. Qiu Y, Wu Y, Zhao H, et al. Maresin 1 mitigates renal ischemia/reperfusion injury in mice via inhibition of the TLR4/MAPK/NF-kappaB pathways and activation of the Nrf2 pathway. Drug Des Devel Ther, 2019, 13: 739-745.
6. Jin SW, Chen HJ, Li YS, et al. Maresin 1 improves the Treg/Th17 imbalance in rheumatoid arthritis through miR-21. Ann Rheum Dis, 2018, 77(11): 1644-1652.
7. Wang H, Shi P, Huang C, et al. Maresin 1 ameliorates iron-deficient anemia in IL-10(-/-) mice with spontaneous colitis by the inhibition of hepcidin expression though the IL-6/STAT3 pathway. Am J Transl Res, 2016, 8(6): 2758-2766.
8. Gong J, Wu ZY, Qi H, et al. Maresin 1 mitigates LPS-induced acute lung injury in mice. Br J Pharmacol, 2014, 171(14): 3539-3550.
9. Liu X, Shen JW, Fan DP, et al. Yupingfeng San inhibits NLRP3 inflammasome to attenuate the inflammatory response in asthma mice. Front Pharmacol, 2017, 8: 944.
10. Pu Y, Liu YQ, Liao SP, et al. Azithromycin ameliorates OVA-induced airway remodeling in Balb/c mice via suppression of epithelial-to-mesenchymal transition. Int Immunopharmacol, 2018, 58: 87-93.
11. Fahy JV. Type 2 inflammation in asthma--present in most, absent in many. Nat Rev Immunol, 2015, 15(1): 57-65.
12. Kuhl K, Hanania NA. Targeting IgE in asthma. Curr Opin Pulm Med, 2012, 18(1): 1-5.
13. Krishnamoorthy N, Burkett PR, Dalli J, et al. Cutting edge: maresin-1 engages regulatory T cells to limit type 2 innate lymphoid cell activation and promote resolution of lung inflammation. J Immunol, 2015, 194(3): 863-867.
14. Zhang Q, Wang LR, Chen BH, et al. Propofol inhibits NF-kappaB activation to ameliorate airway inflammation in ovalbumin (OVA)-induced allergic asthma mice. Int Immunopharmacol, 2017, 51: 158-164.
15. Shin IS, Jeon WY, Shin HK, et al. Effects of montelukast on subepithelial/peribronchial fibrosis in a murine model of ovalbumin induced chronic asthma. Int Immunopharmacol, 2013, 17(3): 867-873.
16. Cargnello M, Roux PP. Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev, 2011, 75(1): 50-83.
17. Yin CY, Bai QF, Feng JX. MiR-216a-5p protects 16HBE cells from H₂O₂-induced oxidative stress through targeting HMGB1/NF-kB pathway. Biochem Biophys Res Commun, 2019, 508(2): 416-420.
18. Goh FY, Upton N, Guan S, et al. Fisetin, a bioactive flavonol, attenuates allergic airway inflammation through negative regulation of NF-kappaB. Eur J Pharmacol, 2012, 679(1-3): 109-116.
19. Goplen N, Karim Z, Guo L, et al. ERK1 is important for Th2 differentiation and development of experimental asthma. FASEB J, 2012, 26(5): 1934-1945.
20. Schieven GL. The biology of p38 kinase: a central role in inflammation. Curr Top Med Chem, 2005, 5(10): 921-928.
21. Zhang LL, Chen B, Fan XY, et al. LPS cooperates with poly-L-arginine to promote IL-6 and IL-8 release via the JNK signaling pathway in NCI-H292 cells. J Immunol Res, 2016, 2016: 3421060.
22. Wang X, Tanino Y, Sato S, et al. Secretoglobin 3A2 attenuates lipopolysaccharide-induced inflammation through inhibition of ERK and JNK pathways in bronchial epithelial cells. Inflammation, 2015, 38(2): 828-834.
23. Lee WH, Yoo HY, Kim JA, et al. Barrier protective effects of piperlonguminine in LPS-induced inflammation in vitro and in vivo. Food Chem Toxicol, 2013, 58: 149-157.
24. Li J, Kartha S, Iasvovskaia S, et al. Regulation of human airway epithelial cell IL-8 expression by MAP kinases. Am J Physiol Lung Cell Mol Physiol, 2002, 283(4): L690-L699.
25. Wang H, Wu Y, Ojcius DM, et al. Leptospiral hemolysins induce proinflammatory cytokines through Toll-like receptor 2-and 4-mediated JNK and NF-kappaB signaling pathways. PLoS One, 2012, 7(8): e42266.

Chinese Journal of Respiratory and Critical Care Medicine

Effect of maresin-1 on lung inflammation and MAPK signaling pathway in asthmatic mice

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