Document Detail


Anti-inflammatory effects in the skin of thymosin-beta4 splice-variants.
MedLine Citation:
PMID:  12709011     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The intraepithelial lymphocyte (IEL) network of T-cell receptor gammadelta+ (Vgamma5+) dendritic epidermal T cells (DETC) in murine skin down-regulates cutaneous inflammation, although the mechanism is unknown. Thymosin-beta4 (Tbeta4), identified by serial analysis of gene expression as a predominant transcript in gut IEL, encodes both a ubiquitous actin-binding protein (UTbeta4) with demonstrated capacity to inhibit neutrophilic infiltration, and a splice-variant limited to lymphoid tissue (LTbeta4) with unknown bioactivity. Freshly isolated Vgamma5+ DETCs expressed both forms, while only LTbeta4 was preferentially up-regulated after cellular activation in vitro. To compare the anti-inflammatory properties of LTbeta4 and UTbeta4 in the skin in vivo, the biological activities of synthesized polypeptides were assessed using three different strategies: neutrophil infiltration by footpad lambda-carrageenan injection; irritant contact dermatitis to 12-O-tetradecanoylphorbol 13-acetate; and allergic contact dermatitis to 2,4-dinitrofluorobenzene. These studies clearly showed that the anti-inflammatory activities of LTbeta4 were broader and most often stronger than those of UTbeta4. Thus, the activation-responsive expression of the lymph-specific form of Tbeta4 may be one mechanism by which DETC, and possibly other IELs, down-regulate local inflammation.
Authors:
Michael Girardi; Michael A Sherling; Renata B Filler; John Shires; Efstathios Theodoridis; Adrian C Hayday; Robert E Tigelaar
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Immunology     Volume:  109     ISSN:  0019-2805     ISO Abbreviation:  Immunology     Publication Date:  2003 May 
Date Detail:
Created Date:  2003-04-23     Completed Date:  2003-06-27     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0374672     Medline TA:  Immunology     Country:  England    
Other Details:
Languages:  eng     Pagination:  1-7     Citation Subset:  IM    
Affiliation:
Department of Dermatology and the Yale Skin Diseases Research Core Center, Yale University, New Haven, Connecticut 06520, USA.
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MeSH Terms
Descriptor/Qualifier:
Alternative Splicing
Animals
Anti-Inflammatory Agents / therapeutic use*
Biological Assay
Cells, Cultured
Dendritic Cells / metabolism*
Dermatitis, Allergic Contact / drug therapy
Dermatitis, Contact / drug therapy*
Dermatitis, Irritant / drug therapy
Female
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Microfilament Proteins / genetics,  metabolism,  therapeutic use*
Receptors, Antigen, T-Cell, gamma-delta / analysis
Skin / metabolism
Thymosin / genetics*
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/Microfilament Proteins; 0/Receptors, Antigen, T-Cell, gamma-delta; 61512-21-8/Thymosin; 77591-33-4/thymosin beta(4)
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