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Regulation of monocyte chemoattractant protein 1 (MCP-1) release by explants of human visceral adipose tissue

Abstract

BACKGROUND:

Monocyte chemoattractant protein-1 (MCP-1) is a chemokine involved in monocyte recruitment during inflammation whose plasma level is elevated in obesity.

OBJECTIVE:

The present studies were designed to examine the release of MCP-1 in primary culture by explants of visceral adipose tissue from morbidly obese women.

RESULTS:

Most of the MCP-1 released by adipose tissue explants was derived from the nonfat cells in adipose tissue. The release of MCP-1 by adipose tissue explants was upregulated almost five-fold between 3 and 48 h of incubation. Approximately half of this upregulation was due to the release of endogenous tumor necrosis factor α (TNFα) and IL-1β based on the ability of a combination of a soluble TNFα receptor (etanercept) and a blocking antibody against IL-1β to reduce MCP-1 release. The release of MCP-1 over 48 h was unaffected by insulin or dexamethasone but significantly reduced by the combination of both agents. MCP-1 release was reduced by 60% in the presence of an inhibitor of the nuclear factor κB (NF-κB) pathway. There were no significant effects of inhibitors of p44/42 mitogen-activated protein kinase (ERK), Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) pathways on MCP-1 release. However, inhibition of MCP-1 release in the presence of inhibitors of both the p38 MAPK and NF-κB pathways was greater than that seen with only the NF-κB inhibitor.

DISCUSSION:

The present data shows that MCP-1 formation is upregulated over a 48-h incubation of primary explants of visceral adipose tissue. Half of this upregulation is dependent upon endogenous TNFα and Il-1β and involves the p38 MAPK and NF-κB pathways.

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Fain, J., Madan, A. Regulation of monocyte chemoattractant protein 1 (MCP-1) release by explants of human visceral adipose tissue. Int J Obes 29, 1299–1307 (2005). https://doi.org/10.1038/sj.ijo.0803032

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