Get started
Work

The Role of MafA in Regulating Cytokine Expression in Pancreatic β Cells

Year: 2011
Type: article
Abstract: Lawrence et al.(1) detail an intriguing discovery in which pancreatic ␤ cells produce cytokines (TNF-␣, TNF-␤, IL-1␤, IFN-␥, and MCP-1) in response to short-term IL-1␤ treatment.This finding suggests that ␤ cells may actively participate in mediating their own failure and apoptosis during the pathogenesis of diabetes.Mechanistically, calcineurin, p38, and JNK are shown to control the ability of NFAT and ATF2/c-Jun to directly regulate the expression of TNF-␣ in ␤ cells.The authors' data also suggest that MafA directly represses TNF-␣ expression in conjunction with C/EBP-␤.Although not discussed by the authors, these data may yield important insight into the role and regulation of MafA in the ␤ cell.Acute high glucose induces, whereas chronic cytokine treatment represses, MafA expression (2-5).However, the role of stimulus-regulated MafA expression has not been elucidated.MafA levels may fluctuate in ␤ cells as a means of controlling the amount of target gene expression that occurs under a given condition (2).The data pre-sented by Lawrence et al. (1) appear to support that model.MafA represses TNF-␣ expression during short-term cytokine treatment (1), but upon chronic cytokine insult, MafA levels decline (3-5), which may relieve the repression of TNF-␣ expression.As such, MafA could indeed accurately regulate the levels of TNF-␣ expression through a stimulus-regulated transcriptional switch mechanism.The glucose-dependent induction of MafA expression may control target gene expression (e. g. insulin expression) in a similar manner.Further experiments will be required to investigate this possibility and to elucidate the underlying mechanism(s).
DOI: 10.1074/jbc.l110.158675
Language: English
Subfield: Surgery
Field: Medicine
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W1996601032
FWCI:
Cites: 5
Cited by:
Related to: 10