Pirfenidone induces intercellular adhesion molecule-1 (ICAM-1) down-regulation on cultured human synovial fibroblasts.
Pirfenidone has been shown to modify some cytokine regulatory actions and inhibit fibroblast biochemical reactions resulting in inhibition of proliferation and collagen matrix synthesis by fibroblast. We have investigated the effect of pirfenidone on the expression of cell adhesion molecules. The synovial fibroblasts were treated with IL-1alpha in the presence or absence of pirfenidone (range 0-1000 microM), and assayed for the expression of adhesion molecules such as ICAM-1 and endothelial-leucocyte adhesion molecule-1 (E-selectin) by cell ELISA. Pirfenidone significantly down-regulated the expression of ICAM-1 on cultured synovial fibroblasts in a dose-dependent manner. In contrast, expression of E-selectin was not affected. Furthermore, we examined whether pirfenidone affects the cellular binding between cultured lymphocytes and IL-1alpha-stimulated synovial fibroblasts by in vitro binding assay and found their mutual binding was significantly suppressed in a dose-dependent manner by pirfenidone. It is speculated that down-regulation of ICAM-1 might be one of the novel mechanisms of action of pirfenidone. These data indicate a novel mechanism of action for pirfenidone to reduce the activation of synovial fibroblasts.
Department of Ophthalmology, Tokyo Dental College, Ichikawa, Japan.
M
M
Kaneko
H
H
Inoue
R
R
Nakazawa
N
N
Azuma
M
M
Suzuki
S
S
Yamauchi
S B
SB
Margolin
K
K
Tsubota
I
I
Saito
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000494:pharmacology; D011728:Pyridones / Q000008:administration & dosage / Q000494:pharmacology*; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007375:Interleukin-1; D011728:Pyridones; D018799:Intercellular Adhesion Molecule-1; C093844:pirfenidone