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ABSTRACT: White adipose tissue exhibits inflammation as tissue mass expands in obesity, involving macrophage infiltration and a direct
inflammatory response by adipocytes. DNA microarrays and conditioned medium have been used to examine the effects of macrophages
on global gene expression in human adipocytes. SGBS adipocytes, differentiated in culture, were treated with macrophage-conditioned
medium (U937 cells) for 4 or 24h; control cells received unconditioned medium. Agilent arrays comprising 44,000 probes were
used to analyse gene expression. Microarray analysis identified 1,088 genes differentially expressed in response to the conditioned
medium at both 4 and 24h (754 up-regulated, 334 down-regulated at 24h); these included genes associated with inflammation
and macrophage infiltration. A cluster of matrix metalloproteinase genes were highly up-regulated at both time-points, including
MMP1, MMP3, MMP9, MMP10, MMP12 and MMP19. At 4 and 24h, MMP1 was the most highly up-regulated gene (>2,400-fold increase in mRNA at 24h). ELISA measurements indicated that substantial
quantities of MMP1 and MMP3 were released from adipocytes incubated with conditioned medium, with little release by control
adipocytes. Treatment with TNFα induced substantial increases in MMP1 (>100-fold) and MMP3 (27-fold) mRNA level and MMP1 and MMP3 release in adipocytes, suggesting that this cytokine could contribute to the stimulation
of MMP expression by macrophages. In conclusion, macrophage-secreted factors induce a major inflammatory response in human
adipocytes, with expression of MMP family members being strongly up-regulated. The induction of MMP1 and other MMPs suggests that macrophages stimulate tissue remodelling during adipose tissue expansion in obesity.
Pflügers Archiv - European Journal of Physiology 04/2012; 458(6):1103-1114. · 4.46 Impact Factor
