Abstract |
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 endoplasmic reticulum (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 the CCN1 IGFbp domain. Functionally, secreted CCN1 promoted anti-inflammatory cytokine interleukin (IL)-10 release from epithelial cells via integrin αVβ6-PKC, and this subsequently suppressed tumor necrosis factor (TNF)-α, macrophage inflammatory protein 2 (MIP-2)-2 secretion and neutrophil infiltration in the lungs. Collectively, bacterial DNA/ CpG ODN-stimulated CCN1 secretion via the 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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Authors | H-G Moon, Z Qin, T Quan, L Xie, C S Dela Cruz, Y Jin |
Journal | Mucosal immunology
(Mucosal Immunol)
Vol. 8
Issue 2
Pg. 243-53
(Mar 2015)
ISSN: 1935-3456 [Electronic] United States |
PMID | 25005359
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, Neoplasm
- CPG-oligonucleotide
- Caveolin 1
- Cysteine-Rich Protein 61
- Cytokines
- DNA, Bacterial
- Endoplasmic Reticulum Chaperone BiP
- Hspa5 protein, mouse
- Inflammation Mediators
- Integrins
- Oligodeoxyribonucleotides
- integrin alphavbeta6
- Interleukin-10
- Proto-Oncogene Proteins pp60(c-src)
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Topics |
- Alveolar Epithelial Cells
(drug effects, metabolism)
- Animals
- Antigens, Neoplasm
(metabolism)
- Caveolin 1
(genetics, metabolism)
- Cysteine-Rich Protein 61
(metabolism)
- Cytokines
(metabolism)
- DNA, Bacterial
(metabolism)
- Disease Models, Animal
- Endoplasmic Reticulum Chaperone BiP
- Endoplasmic Reticulum Stress
- Homeostasis
- Immunity, Innate
- Inflammation Mediators
(metabolism)
- Integrins
(metabolism)
- Interleukin-10
(metabolism)
- Mice
- Mice, Knockout
- Neutrophil Infiltration
- Oligodeoxyribonucleotides
(pharmacology)
- Phosphorylation
- Pneumonia
(immunology, metabolism, pathology)
- Proto-Oncogene Proteins pp60(c-src)
(genetics, metabolism)
- Signal Transduction
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