Bombesin-related peptides modulate interleukin-1 production by alveolar macrophages.
We have tested the effect of bombesin (BN) and BN-related peptides on the production of interleukin-1 (IL-1) by rat alveolar macrophages. BN incubated with AM alone had no direct effect on IL-1 release. However, at concentrations ranging from 10(-11) M to 10(-6) M, BN significantly enhanced IL-1 release by AM activated with lipopolysaccharide (LPS). A typically U-shaped dose-response relationship was observed with maximal effect obtained between 10(-9) M and 10(-8) M. BN also potentiated the stimulatory effects of other IL-1 inducers including muramyl dipeptide (MDP) and granulocyte-macrophage colony stimulating factor (GM-CSF). The 2- to 3-fold enhancement in IL-1 production seen with BN was blocked by the bombesin receptor antagonist [Leu13,-psi(CH2NH)Leu14]-Bombesin. Furthermore, bombesin-related peptides, gastrin-releasing peptides, (GRP)-27 and GRP-10 also potentiated the stimulatory effects of LPS whereas Neuromedin B (NeB) had no effect. These results suggest that BN-related peptides might play an important role as local modulator(s) of cytokine production and inflammatory reactions in the lung.
Lemaire
I
I
Department of Pharmacology, Faculty of Medicine, University of Ottawa, Ontario, Canada.
D000595:Amino Acid Sequence; D000818:Animals; D001839:Bombesin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007375:Interleukin-1 / Q000096:biosynthesis*; D007700:Kinetics; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D051381:Rats; D011919:Rats, Inbred Strains
D007375:Interleukin-1; D001839:Bombesin