Morphine compromises bronchial epithelial TLR2/IL17R signaling crosstalk, necessary for lung IL17 homeostasis

Santanu Banerjee, Jana Ninkovic, Jingjing Meng, Umakant Sharma, Jing Ma, Richard Charboneau, Sabita Roy

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Opportunistic lung infection and inflammation is a hallmark of chronic recreational/clinical use of morphine. We show that early induction of IL17 from the bronchial epithelium, following pathogenic encounter is a protective response, which contributes to pathogenic clearance and currently attributed to TLR2 activation in immune cells. Concurrent activation of TLR2 and IL17R in bronchial epithelium results in the sequestration of MyD88 (TLR2 adapter) by Act1/CIKS (IL17R adapter), thereby turning off TLR2 signaling to restore homeostasis. Morphine inhibits the early IL17 release and interaction between Act1 and MyD88, leading to decreased pathogenic clearance and sustained inflammation. Hence, we propose that therapeutically targeting either TLR2 or IL17 in bronchial epithelia, in the context of morphine, can restore inflammatory homeostasis.

Original languageEnglish (US)
Article number11384
JournalScientific reports
Volume5
DOIs
StatePublished - Jun 15 2015

Bibliographical note

Funding Information:
Grant Support: This work was supported in part by the NIH grants RO1 DA 12104, RO1 DA 022935, RO1 DA031202, K05DA033881, P50 DA 011806 and 1R01DA034582 to SR.

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