Smith, B.W., Hebbard, L., and George, J. (2010) Adiponectin induces pro-infl ammatory cytokines in kupffer cells via the activation of mapk pathways. Journal of Gastroenterology and Hepatology, 25 (s3). A6-A6.

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Abstract

Exogenous adiponectin (Acrp) reduces the severity of CCl4-induced liver fibrosis and has been shown to abrogate LPS-induced cytokine release by Kupffer cells (KCs). We have previously shown that acute Acrp treatment directly stimulates pro-inflammatory and pro-fibrotic cytokine release by KCs, whereas chronic Acrp exposure down regulates this cytokine release in an IL-10-dependent manner. We sought to further characterise then mechanisms which underlie the pro-inflammatory and subsequent anti-inflammatory effects of Acrp.

Methods Primary rat KCs were primed for 18 h with full length Acrp (fl Acrp) or cultured in vehicle only (non-primed KC) prior to being washed and re-treated with flAcrp. A time-course study was then performed and MAPK phospho-protein changes were analysed by Western Blot. To assess the modulatory effects of IL-10 on MAPK pathways, the experiments were repeated in the presence of soluble anti-rat IL-10 antibody or recombinant rat IL-10.

Results In non-primed KCs, flAcrp induced a maximal 46-fold increase in phospho-Erk1/2 and sixfold increase in phospho-p38 at 30 min compared to baseline phosphorylation levels. There was no change in Erk1/2 or p38 phosphorylation in KCs that were primed with flAcrp prior to the time-course study. JNK1/2 phosphorylation was not altered by flAcrp treatment. Recombinant IL-10 abrogated Erk1/2 and p38 phosphorylation in the non-primed KC however the addition of IL-10 antibody had no effect on MAPK phosphorylation in either the primed or non-primed KCs.

Conclusions These observations suggest that acute Acrp exposure mediates acute inflammatory responses in KCs by the activation of MAPK pathways. Chronic Acrp exposure is not associated with MAPK activation; this may be a result of IL-10 acting directly to prevent MAPK activation.

Item ID:	86245
Item Type:	Article (Abstract)
ISSN:	1440-1746
Copyright Information:	© 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd .
Date Deposited:	22 Jul 2025 01:13
FoR Codes:	32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320209 Gastroenterology and hepatology @ 100%
SEO Codes:	20 HEALTH > 2001 Clinical health > 200101 Diagnosis of human diseases and conditions @ 100%
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