PMID- 17505301
OWN - NLM
STAT- MEDLINE
DCOM- 20070720
LR  - 20181113
IS  - 1073-2322 (Print)
IS  - 1540-0514 (Electronic)
IS  - 1073-2322 (Linking)
VI  - 27
IP  - 6
DP  - 2007 Jun
TI  - The priming effect of C5a on monocytes is predominantly mediated by the p38 MAPK 
      pathway.
PG  - 623-30
AB  - The dysregulation of the inflammatory response after trauma leads to significant 
      morbidity and mortality. Monocytes and macrophages play a central role in the 
      orchestration of the inflammatory response after injury. Serum interleukin-6 
      (IL-6) concentration correlates with poor outcomes after injury. Tumor necrosis 
      factor-alpha (TNF-alpha) is a proinflammatory cytokine that plays a crucial role 
      in the pathogenesis of multiple organ dysfunction syndrome. Furthermore, in the 
      presence of C5a, monocytes and macrophages have potentiated responses, but the 
      mechanisms underlying this response remain largely unknown. Peripheral blood 
      mononuclear cells (PBMCs) were isolated from healthy volunteers and pretreated 
      with C5a (100 ng/mL) for 1 h before adding lipopolysaccharide (LPS) (10 ng/mL) 
      for up to 20 h. Inhibitors for the mitogen-activated protein kinases (MAPKs) were 
      added 1 h before adding C5a. C5a primes monocytes for LPS-induced IL-6 and 
      TNF-alpha production. Treatment of PBMCs with C5a leads to a rapid activation of 
      the 3 MAPK pathways. SP600125 (inhibitor of c-Jun NH2-terminal kinase MAPK) and 
      PD98059 (inhibitor of extracellular signal-regulated kinase MAPK) did not affect 
      the C5a priming of the LPS-induced IL-6 and TNF-alpha production, whereas 
      SB203580, a specific inhibitor of p38 MAPK, did suppress the C5a priming effect. 
      These results demonstrate that C5a primes adherent PBMCs and modulates 
      LPS-induced IL-6 and TNF-alpha production. Results from extracellular 
      signal-regulated kinase and c-Jun NH2-terminal kinase MAPK blockade suggest that 
      these signaling pathways have minimal or no role in reprogramming LPS-mediated 
      IL-6 and TNF-alpha production. On the contrary, in PBMCs, C5a activates the p38 
      cascade, and this pathway plays a major role in the C5a enhancement of 
      LPS-induced IL-6 and TNF-alpha production.
FAU - Schaeffer, Valerie
AU  - Schaeffer V
AD  - Department of Surgery, Harborview Medical Center, Seattle, Washington 98104, USA. 
      valschae@u.washington.edu
FAU - Cuschieri, Joseph
AU  - Cuschieri J
FAU - Garcia, Iris
AU  - Garcia I
FAU - Knoll, Megan
AU  - Knoll M
FAU - Billgren, Jens
AU  - Billgren J
FAU - Jelacic, Sandra
AU  - Jelacic S
FAU - Bulger, Eileen
AU  - Bulger E
FAU - Maier, Ronald
AU  - Maier R
LA  - eng
GR  - R01 GM045873/GM/NIGMS NIH HHS/United States
GR  - T32 GM007037/GM/NIGMS NIH HHS/United States
GR  - R01 GM45813/GM/NIGMS NIH HHS/United States
GR  - T32 GM07037/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Shock
JT  - Shock (Augusta, Ga.)
JID - 9421564
RN  - 0 (Imidazoles)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Peptides)
RN  - 0 (Pyridines)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 80295-54-1 (Complement C5a)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - OU13V1EYWQ (SB 203580)
SB  - IM
EIN - Shock. 2018 Jul;50(1):127. PMID: 29677088
MH  - Cell Separation
MH  - Complement C5a/*pharmacology
MH  - Enzyme Activation
MH  - Flow Cytometry
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - Inflammation
MH  - Interleukin-6/metabolism
MH  - Leukocytes, Mononuclear/metabolism
MH  - Lipopolysaccharides/metabolism
MH  - MAP Kinase Signaling System
MH  - Monocytes/*drug effects/metabolism
MH  - Peptides/chemistry
MH  - Pyridines/pharmacology
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
PMC - PMC6014696
MID - NIHMS964829
EDAT- 2007/05/17 09:00
MHDA- 2007/07/21 09:00
PMCR- 2018/06/22
CRDT- 2007/05/17 09:00
PHST- 2007/05/17 09:00 [pubmed]
PHST- 2007/07/21 09:00 [medline]
PHST- 2007/05/17 09:00 [entrez]
PHST- 2018/06/22 00:00 [pmc-release]
AID - 00024382-200706000-00006 [pii]
AID - 10.1097/SHK.0b013e31802fa0bd [doi]
PST - ppublish
SO  - Shock. 2007 Jun;27(6):623-30. doi: 10.1097/SHK.0b013e31802fa0bd.