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Please use this identifier to cite or link to this item:
http://ir.nhri.org.tw/handle/3990099045/9821
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Title: | Cross-regulation of proinflammatory cytokines by interleukin-10 and miR-155 in orientia tsutsugamushi-infected human macrophages prevents cytokine storm |
Authors: | Tsai, MH;Chang, CH;Tsai, RK;Hong, YR;Chuang, TH;Fan, KT;Peng, CW;Wu, CY;Hsu, WL;Wang, LS;Chen, LK;Yu, HS |
Contributors: | Immunology Research Center;National Institute of Environmental Health Sciences |
Abstract: | Scrub typhus is caused by the obligate intracellular bacterium Orientia tsutsugamushi. Macrophages are host cells for its replication and clearance. Severe complications in patients are mainly caused by a cytokine storm resulting from overproduction of proinflammatory cytokines; nevertheless, the molecular mechanism for the occurrence remains obscure. Herein, we investigate the interactive regulation of cytokines and micro-RNA (miR) in human macrophages infected with low and high doses of O. tsutsugamushi. During low dose infection, macrophages produce high levels of IL-10 through extracellular signal-regulated kinase activation, which inhibits proinflammatory cytokine production and facilitates pathogen replication. Increasing levels of pathogen results in reduced levels of IL-10, and macrophages begin to generate high levels of proinflammatory cytokines through NF-κB activation. However, during a high dose infection, macrophages produce high levels of miR-155 to slow the proinflammatory response. The extracellular signal-regulated kinase/IL-10 axis suppresses the NF-κB/tumor necrosis factor alpha axis via activation of signal transducer and activator of transcription 3. Both IL-10 and miR-155 inhibit the NF-κB signaling pathway. Furthermore, IL-10 is a potent inhibitor of miR-155. Patients susceptible to a cytokine storm, peripheral blood mononuclear cells showed significantly lower IL-10 and miR-155 responses to O. tsutsugamushi challenge. Thus, IL-10 and miR-155 operate inhibitory mechanisms to achieve a proper defense mechanism and prevent a cytokine storm. |
Date: | 2016-07 |
Relation: | Journal of Investigative Dermatology. 2016 Jul;136(7):1398-1407. |
Link to: | http://dx.doi.org/10.1016/j.jid.2015.11.034 |
JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-202X&DestApp=IC2JCR |
Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000379016400017 |
Cited Times(Scopus): | http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84983445840 |
Appears in Collections: | [莊宗顯] 期刊論文 [余幸司] 期刊論文
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