Premium
Cyclic stretch induces IL‐8 secretion in human proximal tubular epithelial cells through cPLA 2 , MAPK, and NF‐ κ B signaling pathways
Author(s) -
Pham Khoi M,
Hamzeh Mona T,
Alexander Larry D
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.705.12
Subject(s) - secretion , p38 mitogen activated protein kinases , mapk/erk pathway , signal transduction , chemokine , microbiology and biotechnology , kinase , chemistry , western blot , protein kinase a , phosphorylation , nf κb , extracellular , biology , biochemistry , receptor , gene
Cyclic mechanical stretch represent a unique model to mimic transient increase in intrarenal pressure resulting in tubular mechanical stretch accompanying obstructive nephropathy and may provide a mechanism to stimulate cytokine/chemokine protein expression. The purpose of this study was to investigate the effects of cyclic mechanical stretch on interleukin‐8 (IL‐8) secretion in human proximal tubular epithelial cells (HK‐2). The concentration of IL‐8 was analyzed by ELISA, phosphorylated p38 MAPK, c‐Jun NH2‐terminal kinase (JNK), and extracellular signal‐regulated kinase (ERK1/2) was assessed by Western blot analysis, while nuclear factor‐κB (NF‐κB) was analyzed by an ELISA‐based NF‐κB‐binding assay. Exposure to cyclic mechanical stretch (20%) resulted in a time‐dependent increase in IL‐8 secretion. In addition, we showed that cyclic stretch induced the phosphorylation of p38 MAPK, ERK1/2, and JNK in HK‐2 cells. Cyclic stretch also increased NF‐κB‐binding activities and inhibition of NF‐κB prevented stretch‐induced IL‐8 secretion. Moreover, we showed that selective inhibitors of PLA 2 (Mepacrine), cPLA 2 (MAFP and AACOCF 3 ), ERK1/2 (PD98059), JNK (SP600125), and p38 MAPK, could suppress the effect of cyclic stretch on IL‐8 secretion, which strongly suggests that these pathways play important roles in the stretch‐induced IL‐8 secretion in renal proximal tubular epithelial cells.