Morphine Compromises Bronchial Epithelial TLR2/IL17R Signaling Crosstalk, Necessary for Lung IL17 Homeostasis

Overview

Journal Sci Rep

Specialty Science

Date 2015 Jun 16

PMID 26072707

Citations 8

Authors

Santanu Banerjee

Jana Ninkovic

Jingjing Meng

Umakant Sharma

Jing Ma

Richard Charboneau

Sabita Roy

Affiliations

Soon will be listed here.

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.

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