| CXCL1 regulates pulmonary host defense to Klebsiella Infection via CXCL2, CXCL5, NF-kappaB, and MAPKs. | |
| | |
MedLine Citation:
|
PMID: 20937845 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Pulmonary bacterial infections are a leading cause of death. Since the introduction of antibiotics, multidrug-resistant Klebsiella pneumoniae became an escalating threat. Therefore, development of methods to augment antibacterial defense is warranted. Neutrophil recruitment is critical to clear bacteria, and neutrophil migration in the lung requires the production of ELR(+) CXC chemokines. Although lung-specific CXCL1/keratinocyte cell-derived chemokine (KC) transgene expression causes neutrophil-mediated clearance of K. pneumoniae, the mechanisms underlying KC-mediated host defense against K. pneumoniae have not been explored. In this study, we delineated the host defense functions of KC during pulmonary K. pneumoniae infection using KC(-/-) mice. Our findings demonstrate that KC is important for expression of CXCL2/MIP-2 and CXCL5/LPS-induced CXC chemokine, and activation of NF-κB and MAPKs in the lung. Furthermore, KC derived from both hematopoietic and resident cells contributes to host defense against K. pneumoniae. Neutrophil depletion in mice before K. pneumoniae infection reveals no differences in the production of MIP-2 and LPS-induced CXC chemokine or activation of NF-κB and MAPKs in the lung. Using murine bone marrow-derived and alveolar macrophages, we confirmed KC-mediated upregulation of MIP-2 and activation of NF-κB and MAPKs on K. pneumoniae infection. Moreover, neutralizing KC in bone marrow-derived macrophages before K. pneumoniae challenge decreases bacteria-induced production of KC and MIP-2, and activation of NF-κB and MAPKs. These findings reveal the importance of KC produced by hematopoietic and resident cells in regulating pulmonary host defense against a bacterial pathogen via the activation of transcription factors and MAPKs, as well as the expression of cell adhesion molecules and other neutrophil chemoattractants. |
| | |
Authors:
|
Shanshan Cai; Sanjay Batra; Sergio A Lira; Jay K Kolls; Samithamby Jeyaseelan |
Related Documents
:
|
19542465 - Ll-37 complexation with glycosaminoglycans in cystic fibrosis lungs inhibits antimicrob... 20009665 - Predictive modeling and inflammatory biomarkers in rats with lung contusion and gastric... 3447885 - Compartmental origin of pulmonary macrophages harvested from mechanically disrupted lun... 20576885 - Reconstituting organ-level lung functions on a chip. 21197655 - Cardiac function and disease: emerging role of small ubiquitin-related modifier. 21193035 - Mast cell activation and autism. |
Publication Detail:
|
Type: Journal Article; Research Support, American Recovery and Reinvestment Act; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-10-11 |
Journal Detail:
|
Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 185 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Nov |
Date Detail:
|
Created Date: 2010-11-04 Completed Date: 2010-12-02 Revised Date: 2011-11-21 |
Medline Journal Info:
|
Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
|
Languages: eng Pagination: 6214-25 Citation Subset: AIM; IM |
Affiliation:
|
Department of Pathobiological Sciences,Louisiana State University, Baton Rouge, LA 70803, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Blotting, Western Chemokine CXCL1 / immunology* Chemokine CXCL2 / biosynthesis, immunology Chemokine CXCL5 / biosynthesis, immunology Enzyme Activation / immunology Enzyme-Linked Immunosorbent Assay Gene Expression Regulation / immunology* Intercellular Adhesion Molecule-1 / biosynthesis Klebsiella Infections / immunology* Lung Diseases / immunology*, microbiology* Mice Mice, Inbred C57BL Mice, Knockout Mitogen-Activated Protein Kinases / biosynthesis, immunology NF-kappa B / biosynthesis, immunology Vascular Cell Adhesion Molecule-1 / biosynthesis |
| Grant Support | |
ID/Acronym/Agency:
|
R01 HL-091958/HL/NHLBI NIH HHS; R01 HL-091958S1/HL/NHLBI NIH HHS; R01 HL091958-01/HL/NHLBI NIH HHS; R01 HL091958-01S1/HL/NHLBI NIH HHS; R01 HL091958-02/HL/NHLBI NIH HHS; R01 HL091958-03/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Chemokine CXCL1; 0/Chemokine CXCL2; 0/Chemokine CXCL5; 0/NF-kappa B; 0/Vascular Cell Adhesion Molecule-1; 126547-89-5/Intercellular Adhesion Molecule-1; EC 2.7.11.24/Mitogen-Activated Protein Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Inducible microRNA-155 feedback promotes type I IFN signaling in antiviral innate immunity by target...
Next Document: Memory T cells are enriched in lymph nodes of selectin-ligand-deficient mice.