House Dust Mite Allergen Inhibits Constitutive Neutrophil Apoptosis by Cytokine Secretion via PAR2/PKCδ/p38 MAPK Pathway in Allergic Lymphocytes
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Neutrophils and lymphocytes are essential inflammatory cells in the pathogenesis of allergy. In this study, we evaluated the role of house dust mite (HDM) in the interaction between allergic lymphocytes and neutrophils. The extract of Dermatophagoides pteronissinus (DP) showed a stronger anti-apoptotic impact on neutrophil apoptosis in the coculture of allergic neutrophils with allergic lymphocytes when compared with that in allergic neutrophils alone. DP increased IL-6, IL-8, MCP-1, and GM-CSF in allergic lymphocytes, and the increased cytokines were inhibited by rottlerin—an inhibitor of the protein kinase C (PKC) δ, as well as by SB202190—a p38 MAPK inhibitor. DP activated p38 MAPK in a time-dependent manner. The activation of p38 MAPK was suppressed by PAR2i, which is a protease-activated receptor (PAR) 2 inhibitor, and rottlerin. Both aprotinin—a serine protease inhibitor—and E64—a cysteine protease inhibitor—were not effective on cytokine secretion of lymphocytes. These results, despite increased cytokines in allergic lymphocytes via DP, did not show any differences between asthma and allergic rhinitis. Molecules, including cytokines, released by DP in lymphocytes inhibited the migration of neutrophils. This finding may further elucidate the pathogenic mechanism of allergic diseases due to HDM.
Abstract
Neutrophils and lymphocytes are essential inflammatory cells in the pathogenesis of allergy. In this study, we evaluated the role of house dust mite (HDM) in the interaction between allergic lymphocytes and neutrophils. The extract of Dermatophagoides pteronissinus (DP) showed a stronger anti-apoptotic impact on neutrophil apoptosis in the coculture of allergic neutrophils with allergic lymphocytes when compared with that in allergic neutrophils alone. DP increased IL-6, IL-8, MCP-1, and GM-CSF in allergic lymphocytes, and the increased cytokines were inhibited by rottlerin—an inhibitor of the protein kinase C (PKC) δ, as well as by SB202190—a p38 MAPK inhibitor. DP activated p38 MAPK in a time-dependent manner. The activation of p38 MAPK was suppressed by PAR2i, which is a protease-activated receptor (PAR) 2 inhibitor, and rottlerin. Both aprotinin—a serine protease inhibitor—and E64—a cysteine protease inhibitor—were not effective on cytokine secretion of lymphocytes. These results, despite increased cytokines in allergic lymphocytes via DP, did not show any differences between asthma and allergic rhinitis. Molecules, including cytokines, released by DP in lymphocytes inhibited the migration of neutrophils. This finding may further elucidate the pathogenic mechanism of allergic diseases due to HDM.
참고문헌 (20)
- Friedmann PS, "The role of dust mite antigen sensitization and atopic dermatitis", Clin Exp Allergy, 29, pp.869~872 (1999)
- Holgate ST, "Pathogenesis of asthma", Clin Exp Allergy, 38(6), pp.872~897 (2008)
- 강보경, "The House dust Mite Allergen, Dermatophagoides pteronyssinus Regulates the Constitutive Apoptosis and Cytokine Secretion of Human Eosinophils", 대한의생명과학회지, 20(1), pp.39~42 (2014), 대한의생명과학회
- 김인식, "Effect of House Dust Mite and CCL2 on S100A8 and S100A9 Expression in Human Monocytes", 대한의생명과학회지, 19(4), pp.344~347 (2013), 대한의생명과학회
- 김인식, "Der p 1 Inhibits Spontaneous Neutrophil Apoptosis by Cytokine Secretion of Normal and Allergic Lymphocytes", 대한임상검사과학회지, 47(4), pp.230~236 (2015), 대한임상검사과학회
- Jacquet A, "The role of innate immunity activation in house dust mite allergy", Trends Mol, 17(10), pp.604~611 (2011)
- Tsai JJ, "Mite allergen Der-p2 triggers human B lymphocyte activation and Toll-like receptor-4 induction", PLoS One, 6(9), pp.e23249~ (2011)
- Yang EJ, "Differential effect of CCL2 on constitutive neutrophil apoptosis between normal and asthmatic subjects", J Cell Physiol, 227(6), pp.2567~2577 (2012)
- Kim DH, "House dust mite allergen regulates constitutive apoptosis of normal and asthmatic neutrophils via toll-like receptor 4", PLoS One, 10, pp.e0125983~ (2015)
- Kim EH, "Regulation of constitutive neutrophil apoptosis due to house dust mite allergen in normal and allergic rhinitis subjects", PLoS One, 9, pp.e105814~ (2014)
- Takizawa H, "Bronchial epithelial cells in allergic reactions", Curr Drug Targets Inflamm Allergy, 4(3), pp.305~311 (2005)
- Rossi D, "The biology of chemokines and their receptors", Annu Rev Immunol, 18, pp.217~242 (2000)
- Shakoory B, "The role of human mast cell-derived cytokines in eosinophil biology", J Interferon Cytokine Res, 24, pp.271~281 (2004)
- Lee NR, "House dust mite allergen suppresses neutrophil apoptosis by cytokine release via PAR2 in normal and allergic lymphocytes", Immunol Res, 64(1), pp.123~132 (2016)
- 이상은, "Asthma, mast cells, mediators, allergy", Yonsei Medical Journal, 51(6), pp.808~822 (2010), 연세대학교의과대학
- Walker JK, "Role for -arrestin in mediating paradoxical 2AR and PAR2 signaling in asthma", Curr Opin Pharmacol, 16, pp.142~147 (2014)
- Samokhin GP, "Effects of protein kinase C inhibitors on thromboxane production by thrombin-stimulated platelets", Eur J Pharmacol, 386(2-3), pp.297~303 (1999)
- van der Merwe JQ, "Protease-activated receptor-2 stimulates intestinal epithelial chloride transport through activation of PLC and selective PKC isoforms", Am J Physiol Gastrointest Liver Physiol, 296(6), pp.G1258~G1266 (2009)
- Thomas WR, "House dust mite allergens in asthma and allergy", Trends Mol Med, 16(7), pp.321~328 (2010)
- Gregory LG, "Orchestrating house dust mite-associated allergy in the lung", Trends Immunol, 32(9), pp.402~411 (2011)