Signaling pathway triggered by a short immunomodulating peptide on human monocytes.
A short synthetic peptide (Pa) containing a structural motif ("2-6-11" motif) present in a number of human extracellular matrix proteins was found to stimulate the production of cytokines IL-1alpha, IL-1beta, IL-6, and TNFalpha by human peripheral blood mononuclear cells. We have now investigated the signal transduction pathway involved in the elicitation of these immunomodulating properties on isolated human monocytes. Our results show that active peptide Pa provoked phosphoinositide hydrolysis, intracellular calcium elevation, and cAMP accumulation. Herbimycin A, an inhibitor of protein tyrosine kinases (PTK), markedly reduced these effects of peptide Pa. We have also found that this peptide stimulated CREB, NF-kappaB, and AP-1 DNA-binding activity. With the help of inhibitors of PTK (herbimycin A), phospholipase C (neomycin sulfate), protein kinase C (bis-indolyl maleimide), protein kinase A (H89), and the calmodulin antagonist W-7, as well as cholera toxin, an agent that increases intracellular cAMP, we showed that cytokine (IL-1alpha, IL-1-beta, IL-6, and TNFalpha) production could be modified by the signal transduction pathway triggered by peptide Pa on monocytes.
López-Zabalza
M J
MJ
Department of Biochemistry, University of Navarra, Pamplona, Spain.
Martínez-Lausín
S
S
Bengoechea-Alonso
M T
MT
López-Moratalla
N
N
González
A
A
Santiago
E
E
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000328:Adult; D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008969:Molecular Sequence Data; D009000:Monocytes / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000502:physiology*; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015290:Second Messenger Systems; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism
D000276:Adjuvants, Immunologic; D017362:Cyclic AMP Response Element-Binding Protein; D016207:Cytokines; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D010455:Peptides; D018808:Transcription Factor AP-1; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D011505:Protein-Tyrosine Kinases; D002118:Calcium