Document Detail


Kruppel-like factor 2 (KLF2) regulates monocyte differentiation and functions in mBSA and IL-1β-induced arthritis.
MedLine Citation:
PMID:  22280353     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Kruppel-like factor 2 (KLF2) plays an important role in the regulation of a variety of immune cells, including monocytes. We have previously shown that KLF2 inhibits proinflammatory activation of monocytes. However, the role of KLF2 in arthritis is yet to be investigated. In the current study, we show that recruitment of significantly greater numbers of inflammatory subset of CD11b(+)F4/80(+)Ly6C+ monocytes to the inflammatory sites in KLF2 hemizygous mice compared to the wild type littermate controls. In parallel, inflammatory mediators, MCP-1, Cox-2 and PAI-1 were significantly up-regulated in bone marrow-derived monocytes isolated from KLF2 hemizygous mice, in comparison to wild-type controls. Methylated-BSA and IL-1β-induced arthritis was more severe in KLF2 hemizygous mice as compared to the littermate wild type controls. Consistent with this observation, monocytes isolated from KLF2 hemizygous mice showed an increased number of cells matured and differentiated towards osteoclastic lineage, potentially contributing to the severity of cartilage and bone damage in induced arthritic mice. The severity of arthritis was associated with the higher expression of proteins such as HSP60, HSP90 and MMP13 and attenuated levels of pPTEN, p21, p38 and HSP25/27 molecules in bone marrow cells of arthritic KLF2 hemizygous mice compared to littermate wild type controls. The data provide new insights and evidences of KLF2-mediated transcriptional regulation of arthritis via modulation of monocyte differentiation and function.
Authors:
M Das; J Lu; M Joseph; R Aggarwal; S Kanji; B K McMichael; B S Lee; S Agarwal; A Ray-Chaudhury; O H Iwenofu; P Kuppusamy; V J Pompili; M K Jain; H Das
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Current molecular medicine     Volume:  12     ISSN:  1875-5666     ISO Abbreviation:  Curr. Mol. Med.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-27     Completed Date:  2012-05-24     Revised Date:  2014-10-24    
Medline Journal Info:
Nlm Unique ID:  101093076     Medline TA:  Curr Mol Med     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  113-25     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Arthritis, Experimental / chemically induced,  immunology*,  radiography
Arthritis, Rheumatoid / chemically induced,  immunology*,  radiography
Bone Marrow / metabolism
Bone and Bones / pathology
Cartilage / pathology
Cell Differentiation / genetics
Inflammation / genetics,  immunology,  metabolism
Inflammation Mediators / metabolism
Interleukin-1beta
Kruppel-Like Transcription Factors / genetics,  metabolism*
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Monocytes / cytology*,  immunology*,  metabolism
Osteoclasts / cytology,  metabolism
Peritoneum / immunology
Serum Albumin, Bovine
Signal Transduction
Grant Support
ID/Acronym/Agency:
K01 AR054114/AR/NIAMS NIH HHS; K01 AR054114/AR/NIAMS NIH HHS; K01 AR054114-01A2/AR/NIAMS NIH HHS; R01 HL086548/HL/NHLBI NIH HHS; R01 HL110630/HL/NHLBI NIH HHS; R01 HL119195/HL/NHLBI NIH HHS; R21 CA143787/CA/NCI NIH HHS; R44 HL092706-01/HL/NHLBI NIH HHS; UL1 RR025755/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Inflammation Mediators; 0/Interleukin-1beta; 0/Klf2 protein, mouse; 0/Kruppel-Like Transcription Factors; 0/Serum Albumin, Bovine
Comments/Corrections

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