Document Detail

Modulation of H+ transport mechanisms by interleukin-1 in isolated bovine articular chondrocytes.
MedLine Citation:
PMID:  16121032     Owner:  NLM     Status:  MEDLINE    
The proinflammatory cytokine interleukin-1 (IL-1) promotes the degradation of articular cartilage by inhibiting matrix synthesis and stimulating degradative enzyme activity. Generation of nitric oxide (NO) in response to IL-1 is implicated in these actions. The catabolic actions of IL-1 can be inhibited by manoeuvres which are predicted to dissipate H+ gradients across the chondrocyte plasma membrane. In the present study, the effects of IL-1 on H+ extrusion from bovine articular chondrocytes were investigated. pH was measured using the H+-sensitive fluorescent dye BCECF. Cells were acidified by ammonium rebound and the contribution of the Na+-H+ exchanger (NHE) and of the vacuolar H+-ATPase to acid extrusion was characterised by ion substitution and inhibitor studies. Overnight (18 h) exposure to IL-1 stimulated acid extrusion in a dose-dependent fashion. This effect represented stimulation of both NHE and the ATPase. Characterisation of the timecourse of this response indicated that, while stimulation of acid extrusion was rapid, effects on the ATPase were only apparent after greater than 8h incubation with the cytokine. In keeping with this observation, the protein synthesis inhibitor cycloheximide abolished the stimulatory effect of IL-1 on ATPase-mediated extrusion. The upregulation of ATPase activity by IL-1 was inhibited by the NOS inhibitor L-NAME and by the NO scavenger PTIO. In cells which had not been exposed to IL-1, treatment with the NO donor SNAP also stimulated acid extrusion by the ATPase. In contrast, NHE activity was not altered by any of these compounds. Taken together, these results imply that IL-1 can stimulate acid extrusion in chondrocytes and that this reflects rapid upregulation of NHE with slower induction of H+-ATPase activity which requires elevated levels of NO. While ATPase induction involves protein synthesis, this process may not constitute synthesis of ATPase proteins per se, but rather of some associated regulatory process.
Amanda L Tattersall; Joseph A Browning; Robert J Wilkins
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology     Volume:  16     ISSN:  1015-8987     ISO Abbreviation:  Cell. Physiol. Biochem.     Publication Date:  2005  
Date Detail:
Created Date:  2005-08-25     Completed Date:  2005-11-02     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9113221     Medline TA:  Cell Physiol Biochem     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  43-50     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2005 S. Karger AG, Basel.
University Laboratory of Physiology, Parks Road, Oxford, OX1 3PT, UK.
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MeSH Terms
Cartilage, Articular / cytology,  drug effects,  metabolism
Chondrocytes / drug effects*,  metabolism*
Hydrogen-Ion Concentration
Interleukin-1 / pharmacology*
Ion Transport / drug effects*
Recombinant Proteins / pharmacology
Sodium-Hydrogen Antiporter / metabolism
Vacuolar Proton-Translocating ATPases / metabolism
Reg. No./Substance:
0/Interleukin-1; 0/Recombinant Proteins; 0/Sodium-Hydrogen Antiporter; EC 3.6.1.-/Vacuolar Proton-Translocating ATPases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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