PMID- 14633128
OWN - NLM
STAT- MEDLINE
DCOM- 20040716
LR  - 20171116
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 64
IP  - 6
DP  - 2003 Dec
TI  - Major involvement of CD40 in the regulation of chemokine secretion from human 
      peritoneal mesothelial cells.
PG  - 2064-71
AB  - BACKGROUND: CD40 is a member of the tumor necrosis factor (TNF) family of 
      receptors, whose ligand, CD154, is expressed by activated mononuclear cells. CD40 
      activation is a major immune regulatory pathway and is important for the 
      regulation of chemokine and cytokine secretion. This study investigates the 
      effect of CD40 ligation on the secretion of chemokines from human peritoneal 
      mesothelial cells (HPMC). METHODS: We activated CD40 in HPMC along with 
      combinations of TNF-alpha, interleukin-1 (IL-1), and interferon gamma 
      (IFN-gamma), and evaluated the mRNA levels and protein secretion of regulated 
      upon activation, normal T-cell expressed and secreted (RANTES), monocyte 
      chemoattractant protein-1 (MCP-1), and IL-8. RESULTS: CD40 ligation had a small 
      stimulatory effect on the secretion of all three chemokines, while TNF-alpha, 
      IL-1 and IFN-gamma induced their secretion in a dose-dependent manner. The 
      combination of CD40 ligation with either IL-1 or TNF-alpha increased chemokine 
      secretion additively. IFN-gamma and CD40 ligation acted in synergy to induce the 
      secretion of the mononuclear recruiting chemokines RANTES and MCP-1 (up to 
      approximately 36-fold and approximately threefold, respectively), for which the 
      combination of all three cytokines with CD40 ligation was extremely potent. In 
      contrast, the secretion of the neutrophil chemoattractant IL-8, induced by CD40 
      ligation or by the combination of IL-1 and TNF-alpha, was reduced in the presence 
      of IFN-gamma. CONCLUSION: In light of our data, it is reasonable to suggest that 
      in the mononuclear phase of peritonitis, IFN-gamma and CD154, expressed by 
      activated mononuclear cells, diminish IL-8 secretion from HPMC and thus inhibit 
      neutrophil recruitment. At the same time, the two act in synergy to induce the 
      secretion of RANTES and MCP-1 from HPMC. Hence, by regulating chemokine 
      secretion, CD40 may be involved in peritonitis and in the development of late 
      phase mononuclear predominance.
FAU - Man, Limor
AU  - Man L
AD  - Department of Nephrology, Soroka University Medical Center, Ben-Gurion University 
      of the Negev, Faculty of Health Sciences, Beer-Sheva, Israel.
FAU - Lewis, Eli
AU  - Lewis E
FAU - Einbinder, Tom
AU  - Einbinder T
FAU - Rogachev, Boris
AU  - Rogachev B
FAU - Chaimovitz, Cidio
AU  - Chaimovitz C
FAU - Douvdevani, Amos
AU  - Douvdevani A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (CD40 Antigens)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Drug Combinations)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-8)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - CD40 Antigens/*physiology
MH  - Cells, Cultured
MH  - Chemokine CCL2/*metabolism
MH  - Chemokine CCL5/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Drug Combinations
MH  - Drug Synergism
MH  - Epithelial Cells/metabolism
MH  - Humans
MH  - Interferon-gamma/administration & dosage/pharmacology
MH  - Interleukin-1/administration & dosage/pharmacology
MH  - Interleukin-8/*metabolism
MH  - Mice
MH  - Peritoneum/cytology/*metabolism
MH  - Tumor Necrosis Factor-alpha/administration & dosage/pharmacology
EDAT- 2003/11/25 05:00
MHDA- 2004/07/17 05:00
CRDT- 2003/11/25 05:00
PHST- 2003/11/25 05:00 [pubmed]
PHST- 2004/07/17 05:00 [medline]
PHST- 2003/11/25 05:00 [entrez]
AID - S0085-2538(15)49574-2 [pii]
AID - 10.1046/j.1523-1755.2003.00338.x [doi]
PST - ppublish
SO  - Kidney Int. 2003 Dec;64(6):2064-71. doi: 10.1046/j.1523-1755.2003.00338.x.