Matrix protein CCN1 induced by bacterial DNA and CpG ODN limits lung inflammation and contributes to innate immune homeostasis.
Matrix protein CCN1 induced by bacterial DNA and CpG ODN limits lung inflammation and contributes to innate immune homeostasis.
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作者：
To defend against pulmonary infections, lung epithelial cells are equipped with complex innate immunity closely linked to inflammation. Dysregulated innate immunity / inflammation leads to self-perpetuating lung injury. The CpG motif in bacterial DNA is one of the factors involved in bacterial infection-associated inflammation. Bacterial DNA and synthetic CpG oligonucleotide (ODN) induced CCN1 secretion from lung epithelial cells, functioning as a potential “braking” signal to prevent uncontrolled inflammatory responses. CpG ODN-induced ER stress resulted in Src-Y527 phosphorylation (pY527) and Src/CCN1 vWF domain dissociation. Src-Y527 activated caveolin-1 (cav-1) phosphorylation at Y14 and then modulated CCN1 secretion via pCav-1 interaction with CCN1 IGFbp domain. Functionally, secreted CCN1 promoted anti-inflammatory cytokine IL-10 release from epithelial cells via integrin αVβ6 PKC, and this subsequently suppressed TNF-α, MIP-2 secretion and neutrophil infiltration in the lungs. Collectively, bacterial DNA/CpG ODN-stimulated CCN1 secretion via BiP/GRP78-Src(Y527)-JNK-Cav-1(Y14) pathway and CpG-induced CCN1 conferred anti-inflammatory roles. Our studies suggested a novel paradigm by which the lung epithelium maintains innate immune homeostasis after bacterial infection.
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影响因子：
4.6
作者：
Kim, Hee Jung;Jeong, Jae Seok;Kim, So Ri;Park, Seung Yong;Chae, Han Jung;Lee, Yong Chul
通讯作者：
Lee, Yong Chul
DOI：
10.1152/ajplung.00102.2012
发表时间：
2012-11-01
影响因子：
4.9
作者：
An, Chang Hyeok;Wang, Xiao Mei;Choi, Augustine M. K.
通讯作者：
Choi, Augustine M. K.
影响因子：
2.7
作者：
Minhas, Uzma;Martin, Tracey A.;Jiang, Wen G.
通讯作者：
Jiang, Wen G.
影响因子：
5.8
作者：
Martinon F
通讯作者：
Martinon F
影响因子：
7.4
作者：
Gewandter, Jennifer S.;Staversky, Rhonda J.;O'Reilly, Michael A.
通讯作者：
O'Reilly, Michael A.