PMID- 15308470
OWN - NLM
STAT- MEDLINE
DCOM- 20050308
LR  - 20171116
IS  - 0193-1857 (Print)
IS  - 0193-1857 (Linking)
VI  - 288
IP  - 1
DP  - 2005 Jan
TI  - Disruption of CD40-CD40 ligand pathway inhibits the development of intestinal 
      muscle hypercontractility and protective immunity in nematode infection.
PG  - G15-22
AB  - In our previous studies, we demonstrated that during Trichinella spiralis 
      infection, T helper (Th) 2 cells contribute to the development of intestinal 
      muscle hypercontractility and worm expulsion from the gut via STAT6. In addition, 
      we have linked the altered muscle contractility to the eviction of the parasite 
      and thereby to the host defense. However, the initial events linking infection to 
      the development of muscle hypercontractility are poorly understood. In this 
      study, we examined the contribution of CD40-CD40 ligand (CD40L) interaction in 
      the development of intestinal muscle hypercontractility, in monocyte 
      chemoattractant protein-1 (MCP-1) production, and in the Th2 response in CD40 
      ligand-deficient (CD40L -/-) mice infected with T. spiralis. Expulsion of 
      intestinal worms was substantially delayed in CD40L -/- mice compared with the 
      wild-type mice after T. spiralis infection. Consistent with delayed worm 
      expulsion, there was a significant attenuation of intestinal muscle contractility 
      in CD40L -/- mice. Infected CD40L -/- mice also exhibited marked impairment in 
      the production of MCP-1, IL-4, IL-13, IgG1, IgE, and mouse mucosal MCP 1 
      (MMCP-1), and in goblet cell response. These results demonstrate that CD40-CD40 
      ligand interaction plays an important role in MCP-1 production, Th2 response, 
      intestinal muscle hypercontractility, and worm expulsion in nematode infection. 
      The present data suggest that the early events leading to the generation of Th2 
      response include CD40-CD40 ligand interaction, which subsequently influences the 
      production of Th2 cytokines, most likely via upregulation of MCP-1.
FAU - Khan, W I
AU  - Khan WI
AD  - Intestinal Disease Research Program, Department of Medicine, McMaster University, 
      Hamilton, Ontario L8N 3Z5, Canada.
FAU - Motomura, Y
AU  - Motomura Y
FAU - Blennerhassett, P A
AU  - Blennerhassett PA
FAU - Kanbayashi, H
AU  - Kanbayashi H
FAU - Varghese, A K
AU  - Varghese AK
FAU - El-Sharkawy, R T
AU  - El-Sharkawy RT
FAU - Gauldie, J
AU  - Gauldie J
FAU - Collins, S M
AU  - Collins SM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040812
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (CD40 Antigens)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 147205-72-9 (CD40 Ligand)
SB  - IM
MH  - Animals
MH  - CD40 Antigens/*immunology
MH  - CD40 Ligand/*immunology
MH  - Chemokine CCL2/biosynthesis/pharmacology
MH  - Cytokines/biosynthesis
MH  - Digestive System/*immunology/*parasitology
MH  - Disease Models, Animal
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Muscle Contraction/*immunology
MH  - Muscle, Smooth/physiology
MH  - T-Lymphocytes, Helper-Inducer/immunology
MH  - Trichinella/*pathogenicity
MH  - Trichinellosis/*immunology/veterinary
MH  - Up-Regulation
EDAT- 2004/08/17 10:00
MHDA- 2005/03/09 09:00
CRDT- 2004/08/17 10:00
PHST- 2004/08/17 10:00 [pubmed]
PHST- 2005/03/09 09:00 [medline]
PHST- 2004/08/17 10:00 [entrez]
AID - 00159.2004 [pii]
AID - 10.1152/ajpgi.00159.2004 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2005 Jan;288(1):G15-22. doi: 
      10.1152/ajpgi.00159.2004. Epub 2004 Aug 12.