Palmitic acid induces IP-10 expression in human macrophages via NF-kappaB activation.
It is now recognized that cross-talk between adipocytes and adipose tissue stromal cells such as macrophages contributes to local and systemic inflammation. One factor from adipocytes that may participate in this interaction and that is frequently elevated in inflammatory conditions such as obesity, insulin resistance, and type 2 diabetes is free fatty acids (FFA). To investigate the potential for FFA to enhance macrophage inflammation, we exposed U937 macrophages to physiological levels (150 microM) of FFA. Palmitic acid (PA), the predominant saturated FFA released from adipose tissue, but not unsaturated FFA, induced an approximately 6-fold (p<0.05) increase in IP-10 gene expression (and 2- to 4-fold increases in IL-8, MCP-1, COX-2, and MIG). PA also induced an approximately 2-fold increase (p<0.05) in active NF-kappaB, and two structurally distinct NF-kappaB inhibitors effectively blocked PA-induced IP-10 gene expression. Conditioned medium from PA-treated cells increased lymphocyte migration 41% (p<0.05) which was significantly reduced by IP-10-neutralizing antibody. These results suggest that elevated concentrations of PA commonly present in obese and insulin resistant individuals can increase NF-kappaB-mediated expression of IP-10 in macrophages. These events in turn may lead to an increasing feed-forward loop of chronic inflammation.
Laine
Phyllis S
PS
Department of Medicine, Division of Endocrinology, Carl T. Hayden VA Medical Center, Phoenix, AZ 85012, USA.
Schwartz
Eric A
EA
Wang
Yingjie
Y
Zhang
Wei-Yang
WY
Karnik
Sheetal K
SK
Musi
Nicolas
N
Reaven
Peter D
PD
D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D019308:Palmitic Acid / Q000494:pharmacology*
C111835:CCL2 protein, human; C114753:CXCL10 protein, human; C080810:CXCL9 protein, human; D018932:Chemokine CCL2; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D005230:Fatty Acids, Nonesterified; D016209:Interleukin-8; D008565:Membrane Proteins; D016328:NF-kappa B; D019308:Palmitic Acid; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human