Cysteinyl-leukotriene D4 induced IL-1 beta expression and release in rat vascular smooth muscle cells.
Vascular cells, including smooth muscle cells (VSMC), may release interleukin 1 (IL-1) and transcribe its genes for both isoforms. Previous studies have shown that cysteinyl-leukotrienes can modulate cytokine production by monocytes and a cytokine-eicosanoid network has been suggested during atherosclerosis. In this study the effects of cysteinyl-leukotriene D4 (LTD4) on IL-1 beta production and IL-1 beta mRNA expression were tested on rat VSMC. LTD4 showed a significant dose-dependent (from basal production of 55 +/- 15 pg/ml to maximal production of 177 +/- 14 pg/ml) and time-dependent (peaking at 24 h 16 +/- 54 pg/ml) increase of IL-1 beta immunoreactivity in the supernatants of conditioned medium and cell lysates. Furthermore, LTD4 induced an increased mRNA expression which began at 1 h and peaked at 12 h incubation time. The production of IL-1 beta was inhibited by MK-571 (from 145 +/- 12 to 60 +/- 10 pg/ml), a specific receptor antagonist of LTD4 and partially reduced by IL-1 receptor antagonist (IL-1 ra) (from 160 +/- 12 to 85 +/- 5 pg/ml). These experiments suggest that cysteinyl-leukotrienes, potentially produced in the vascular wall by leukocytes or by transcellular metabolism, may be involved in local IL-1 production.
Porreca
E
E
Istituto di Patologia Speciale Medica, Ospedale Civile SS Annunziata, Chieti, Italy.
Conti
P
P
Feliciani
C
C
Di Febbo
C
C
Reale
M
M
Mincione
G
G
Neri
M
M
Amerio
P
P
Cuccurullo
F
F
D000704:Analysis of Variance; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D017998:Leukotriene D4 / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011422:Propionates / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors
D007375:Interleukin-1; D011422:Propionates; D011804:Quinolines; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; C059141:verlukast; D017998:Leukotriene D4