title: Role of inositol 1,4,5-triphosphate and p38 mitogen-activated protein kinase in reactive oxygen species generation by granulocytes in a cyclic AMP-dependent manner: an age-related phenomenon.
abstract: BACKGROUND
  It is generally agreed that elderly subjects undergo progressive deterioration of their immune responsiveness, which leads to an increased susceptibility to autoimmune processes, neoplasm and inflammation. Thus there is a general consensus that regulation of inflammation results from a balance between pro-inflammatory and anti-inflammatory pathways.
  
  
  OBJECTIVE
  The present study aimed to investigate the possible alterations of cyclic AMP/protein kinase A (cAMP/PKA) and p38 mitogen-activated protein kinase (p38 MAPK) pathway signaling (reactive oxygen species (ROS) generation) and inositol 1,4,5-triphosphate (InsP3) production by neutrophils during the aging process.
  
  
  METHODS
  Age-induced ROS generation and InsP3 production were studied in healthy subjects ranging in age from 20 to 80 years. The subjects were divided into six age groups: (I) 20-29, (II) 30-39, (III) 40-49, (IV) 50-59, (V) 60-69, and (VI) 70-80 years old. The effect of cAMP, H89 (inhibitor PKA), and PD169316 (inhibitor p38 MAPK) on ROS production was quantified in a luminol-dependent chemiluminescence assay (relative light units/min) and by InsP3 release (cpm).
  
  
  RESULTS
  Our results demonstrated a lack of dibutyryl cAMP inhibitory effects on ROS generation and InsP3 production by granulocytes from PKA-dependent 50-year-olds. However, the inhibitory effect of cAMP is restored in neutrophils after the age of 50 years when p38 MAPK signaling is inhibited.
  
  
  CONCLUSIONS
  The present study may be important towards a better understanding of the high susceptibility to infections and age-related inflammatory and deregulation diseases. The alteration of cAMP/PKA and p38 MAPK signaling pathways enhances the inflammatory process.
authors: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors: Míriam Martins
authors: MM
authors: Chaves
authors: Daniela Caldeira
authors: DC
authors: Costa
authors: Cristina Costa Telhado
authors: CC
authors: Pereira
authors: Thiago Rabelo
authors: TR
authors: Andrade
authors: Bernardo Coelho
authors: BC
authors: Horta
authors: José Augusto
authors: JA
authors: Nogueira-Machado
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D015544:Inositol 1,4,5-Trisphosphate; D017868:Cyclic AMP-Dependent Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases