title: CD38 cleavage in fMLP- and IL-8-induced chemotaxis is dependent on p38 MAP kinase but independent of p44/42 MAP kinase.
abstract: In this study, we examined the mechanism by which CD38 cleavage is regulated through the mitogen-activated protein (MAP) kinases after stimulation by fMLP and interleukin-8 (IL-8) in neutrophils. Both fMLP and IL-8 increased chemotaxis and decreased CD38 protein in neutrophils, but did not change CD38 mRNA levels. Both fMLP and IL-8 increased CD38 in supernatants, which was inhibitable with PMSF. fMLP stimulation resulted in phosphorylation of p38 MAP kinase and p42/44 MAP kinase (ERK). SB20358, a p38 MAP kinase inhibitor, down-regulated neutrophil chemotaxis. Conversely, PD98059, an ERK inhibitor, did not influence chemotaxis to either agonist. The addition of SB20358 blocked the decrease of CD38 on neutrophils and the increase in supernatants induced by fMLP or IL-8, whereas PD98059 did not. These findings suggest that CD38-mediated chemotaxis to fMLP or IL-8 is characterized by proteolytic cleavage of CD38 and signaling through p38 MAP kinase. Activation of the protease for cleavage appears to be a postreceptor event that is dependent on p38 MAP kinase signaling.
authors.affiliation: Department of Periodontology and Oral Biology, Goldman School of Dental Medicine, Boston University, 100 East Newton Street, G-107, Boston, MA 02118, USA.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Fujita
authors.forename: Khalid H
authors.initials: KH
authors.lastname: Zawawi
authors.forename: Hidemi
authors.initials: H
authors.lastname: Kurihara
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Van Dyke
mesh_terms: D036541:ADP-ribosyl Cyclase / Q000235:genetics / Q000378:metabolism*; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D036563:Cyclic ADP-Ribose / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D016209:Interleukin-8 / Q000494:pharmacology*; D008562:Membrane Glycoproteins; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D010455:Peptides / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D044042:Receptors, Formyl Peptide / Q000819:agonists; D044067:Receptors, Lipoxin / Q000819:agonists; D014105:Tosyl Compounds / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D004791:Enzyme Inhibitors; C105101:FPR2 protein, human; D005419:Flavonoids; D007093:Imidazoles; D016209:Interleukin-8; C408903:MMK-1 peptide; D008562:Membrane Glycoproteins; D010455:Peptides; D011725:Pyridines; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; D014105:Tosyl Compounds; D036563:Cyclic ADP-Ribose; C003614:4-toluenesulfonyl fluoride; D009240:N-Formylmethionine Leucyl-Phenylalanine; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one