ABSTRACT
Dendritic cells (DCs) play a key role in activating the immune response against invading pathogens as well as dying cells or tumors. Although the immune response can be initiated by the phagocytic activity by DCs, the molecular mechanism involved in this process has not been fully investigated. Trp-Lys-Tyr-Met-Val-Met-NH2 (WKYMVM) stimulates the activation of phospholipase D (PLD) via Ca2+ increase and protein kinase C activation in mouse DC cell line, DC2.4. WKYMVM stimulates the phagocytic activity, which is inhibited in the presence of N-butanol but not t-butanol in DC2.4 cells. Furthermore, the addition of phosphatidic acid, an enzymatic product of PLD activity, enhanced the phagocytic activity in DC2.4 cells. Since at least two of formyl peptide receptor (FPR) family (FPR1 and FPR2) are expressed in DC2.4 as well as in mouse bone marrow-derived dendritic cells, this study suggests that the activation of FPR family by WKYMVM stimulates the PLD activity resulting in phagocytic activity in DC2.4 cells.
Subject(s)
Animals , Mice , 1-Butanol/pharmacology , Bone Marrow Cells/cytology , Calcium Signaling/drug effects , Cell Death/immunology , Cell Line , Communicable Diseases/immunology , Dendritic Cells/immunology , Neoplasms/immunology , Oligopeptides/pharmacology , Phagocytosis/drug effects , Phosphatidic Acids/pharmacology , Phospholipase D/metabolism , Receptors, Formyl Peptide/metabolism , tert-Butyl Alcohol/pharmacologyABSTRACT
Inflammatory responses are strictly regulated by coordination of pro-inflammatory and anti-inflammatory mediators. Interleukin-4 (IL-4) and interleukin-10 (IL-10) have typically the biologic anti-inflammatory effects on monocytes, but uncertain effects on polymorphonuclear leukocytes (PMNs). The PMNs are the first line of cellular response for host defense during acute inflammation. To modify hyper-inflammatory reaction with biologic anti-inflammatory mediators, we have determined the biologic anti-inflammatory activities of IL-4 and IL-10 on human PMNs. Human PMNs were pretreated with IL-4 or IL-10 and then stimulated with formyl methionyl leucyl phenylalanine (fMLP) for times indicated. The level of H2O2, interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) were determined in the each cell free supernatants. fMLP plays the role of a typical pro-inflammatory agent and, at least in determined conditions, down-regulated TNF release. IL-4 acts as an anti-inflammatory mediator but IL-10 did not show its anti-inflammatory activities on fMLP-stimulated human PMNs. IL-4 and IL-10 have different anti-inflammatory mechanisms. Perhaps, IL-10 needs co-factors to act as an anti-inflammatory mediator.