PMID- 18667484
OWN - NLM
STAT- MEDLINE
DCOM- 20090330
LR  - 20220409
IS  - 1931-857X (Print)
IS  - 1522-1466 (Linking)
VI  - 296
IP  - 2
DP  - 2009 Feb
TI  - IL-8 amplifies CD40/CD154-mediated ICAM-1 production via the CXCR-1 receptor and 
      p38-MAPK pathway in human renal proximal tubule cells.
PG  - F438-45
LID - 10.1152/ajprenal.90214.2008 [doi]
AB  - Activation of the CD40 receptor by its cognate ligand, CD154, results in 
      interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) production 
      and increased intercellular adhesion molecule-1 (ICAM-1) expression in proximal 
      tubule cells (PTCs). The independent role of these two proinflammatory 
      chemokines, IL-8 and MCP-1, in inciting an inflammatory response in PTCs was 
      explored. Exposure of primary cultures of human renal PTCs to recombinant IL-8 
      and MCP-1 resulted in increased ICAM-1 expression measured by quantitative 
      real-time PCR, but confirmed only for IL-8 by immunoblot. The mechanism of action 
      of IL-8 was explored in further detail. Immunohistochemistry identified both the 
      CXCR-1 and CXCR-2 receptors, confirmed by RT-PCR, immunoprecipitation, 
      immunoblot, and FACS analysis. IL-8 increased ICAM-1 expression only via the 
      CXCR-1 receptor, which in turn resulted in activation of the p38 
      mitogen-activated protein kinase (MAPK) pathway; neither the extracellular 
      signal-related kinase (ERK) 1/2 MAPK pathway nor the stress-activated protein 
      kinase (SAPK)/c-Jun NH(2) terminal kinase (JNK) pathway was involved. 
      CD154/CD40-mediated ICAM-1 upregulation was not affected by preincubation of 
      monolayers with the CXCR-1 blocking antibody, indicating that ICAM-1 expression 
      occurs independent of CD154-mediated IL-8 production. Coincubation of monolayers 
      with both CD154 and IL-8 resulted in a greater ICAM-1 response than either 
      compound alone. We conclude that in human renal PTCs, IL-8 upregulates ICAM-1 
      production by engaging the CXCR-1 receptor and p38 MAPK signaling pathway. This 
      cascade of events is independent of CD40/CD154-mediated IL-8 stimulation and 
      ICAM-1 production and serves to amplify the inflammatory response.
FAU - Li, Hongye
AU  - Li H
AD  - Department of Medicine, Div. of Nephrology, School of Medicine, HSC T-16 Rm-080, 
      State Univ. of NY at Stony Brook, Stony Brook, NY 11794, USA.
FAU - Nord, Edward P
AU  - Nord EP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080730
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (CCL2 protein, human)
RN  - 0 (CD40 Antigens)
RN  - 0 (CXCL8 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-8)
RN  - 0 (Receptors, Interleukin-8A)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 147205-72-9 (CD40 Ligand)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - CD40 Antigens/metabolism
MH  - CD40 Ligand/metabolism
MH  - Cells, Cultured
MH  - Chemokine CCL2/*metabolism
MH  - Humans
MH  - Intercellular Adhesion Molecule-1/*metabolism
MH  - Interleukin-8/*metabolism
MH  - Kidney Tubules, Proximal/*metabolism
MH  - MAP Kinase Signaling System
MH  - Receptors, Interleukin-8A/*metabolism
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
EDAT- 2008/08/01 09:00
MHDA- 2009/03/31 09:00
CRDT- 2008/08/01 09:00
PHST- 2008/08/01 09:00 [pubmed]
PHST- 2009/03/31 09:00 [medline]
PHST- 2008/08/01 09:00 [entrez]
AID - 90214.2008 [pii]
AID - 10.1152/ajprenal.90214.2008 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2009 Feb;296(2):F438-45. doi: 
      10.1152/ajprenal.90214.2008. Epub 2008 Jul 30.