Mitogen-activated protein kinase p38 pathway in venous ulcer fibroblasts.
OBJECTIVE
Venous ulcer fibroblasts (w-fb) have attenuated growth compared to normal fibroblasts (n-fb). The MAPKp38 pathway mediates stress-responses in various diseases. We hypothesize that p38 pathway is altered in w-fb.


METHODS
W-fb were isolated from venous ulcers and n-fb from the ipsilateral thigh. Fibroblasts were analyzed for phosphorylated p38 using immunoblot. The relation between p38 and w-fb proliferation was assessed with SB203580 (p38 inhibitor). Fibroblasts were treated with bFGF, TNF-a, and IL-1 and p38 expression analyzed.


RESULTS
Phosphorylated p38 expression was increased in w-fb (AU%=233.5+/-59.7, P=0.039) compared to n-fb (AU%=99.9+/-14.6). W-fb treated with SB203580 demonstrated increased growth compared to untreated w-fb. W-fb treated with bFGF demonstrated decreased p38. TNF-alpha and IL-1beta significantly increase p38 expression.


CONCLUSIONS
MAPK p38 is up-regulated in w-fb. Regulation of w-fb proliferation is influenced by p38. Altering the p38 pathway in vivo with growth factors or cytokine inhibition may improve fibroblast proliferation and venous ulcer healing.
Raffetto
Joseph D
JD
Boston University School of Medicine, MA, USA. joseph.raffetto@med.va.gov
Gram
Christopher H
CH
Overman
Kristen C
KC
Menzoian
James O
JO
D000328:Adult; D000368:Aged; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D014647:Varicose Ulcer / Q000201:enzymology* / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D007093:Imidazoles; D007375:Interleukin-1; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580