PMID- 12970138
OWN - NLM
STAT- MEDLINE
DCOM- 20031209
LR  - 20190501
IS  - 0017-5749 (Print)
IS  - 1458-3288 (Electronic)
IS  - 0017-5749 (Linking)
VI  - 52
IP  - 10
DP  - 2003 Oct
TI  - Inducible CD40 expression mediates NFkappaB activation and cytokine secretion in 
      human colonic fibroblasts.
PG  - 1448-56
AB  - BACKGROUND: CD40 has been shown to be a functional activation antigen on a 
      variety of cell types involved in immune responses. As intestinal fibroblasts and 
      myofibroblasts may play a role during mucosal inflammation, we investigated the 
      functional consequences of CD40 induction in primary cultures of human colonic 
      fibroblasts. METHODS: Primary colonic lamina propria fibroblasts (PCLF) were 
      isolated from endoscopic biopsies and surgical specimens. Cultures were used 
      between passages 3 and 9. CD40 surface display was determined by FACS analysis 
      and mRNA expression by reverse transcription-polymerase chain reaction. Secretion 
      of cytokines was determined by ELISA. Nuclear factor kappaB (NFkappaB) activation 
      was shown by electrophoretic mobility shift assay (EMSA). RESULTS: After priming 
      with interferon gamma (IFN-gamma) (200 U/ml) for 72 hours, five of eight tested 
      PCLF cultures showed induction of CD40 surface display (up to 10-fold). Induction 
      of CD40 mRNA expression was demonstrated by semiquantitative polymerase chain 
      reaction. In the responder-PCLF cultures, IFN-gamma alone caused a 1.5-5-fold 
      increase in interleukin (IL)-8 secretion. Addition of 1 ng/ml CD40L was 
      sufficient to achieve a further increase in IL-8, IL-6, or monocyte chemotactic 
      protein 1 (MCP-1) secretion (2.5-18-fold of controls). Incubation with CD40L 
      alone without priming with IFN-gamma had no effect. The proteasome inhibitor 
      N-acetyl-leucinyl-leucinyl-norleucinal (ALLN 100 microM) reduced IFN-gamma/CD40L 
      mediated cytokine induction, suggesting participation of NFkappaB, which was 
      directly demonstrated by EMSA. CD4+ T cells induced MCP-1 secretion by PCLF, 
      which was prevented by addition of an excess of CD40-IgG fusion protein. CD40 
      expression on PCLF could also be demonstrated in vivo by immunohistochemistry. 
      CONCLUSION: The CD40-CD40L pathway augments mucosal inflammatory responses via 
      mucosal PCLF. CD40-CD40L mediated T cell/PCLF interactions could play an 
      important role during intestinal mucosal inflammation.
FAU - Gelbmann, C M
AU  - Gelbmann CM
AD  - Department of Internal Medicine I, University of Regensburg, Germany.
FAU - Leeb, S N
AU  - Leeb SN
FAU - Vogl, D
AU  - Vogl D
FAU - Maendel, M
AU  - Maendel M
FAU - Herfarth, H
AU  - Herfarth H
FAU - Scholmerich, J
AU  - Scholmerich J
FAU - Falk, W
AU  - Falk W
FAU - Rogler, G
AU  - Rogler G
LA  - eng
PT  - Journal Article
PL  - England
TA  - Gut
JT  - Gut
JID - 2985108R
RN  - 0 (CD40 Antigens)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adult
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - CD40 Antigens/analysis/genetics/*metabolism
MH  - Chemokine CCL2/analysis
MH  - Coculture Techniques
MH  - Colitis, Ulcerative/immunology
MH  - Colon/*immunology
MH  - Crohn Disease/immunology
MH  - Cytokines/*metabolism
MH  - Electrophoretic Mobility Shift Assay
MH  - Fibroblasts/immunology
MH  - Flow Cytometry
MH  - Humans
MH  - Immunohistochemistry/methods
MH  - Interferon-gamma/pharmacology
MH  - Intestinal Mucosa/chemistry
MH  - Middle Aged
MH  - NF-kappa B/immunology/*metabolism
MH  - RNA, Messenger/analysis
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC1773835
EDAT- 2003/09/13 05:00
MHDA- 2003/12/11 05:00
PMCR- 2006/10/01
CRDT- 2003/09/13 05:00
PHST- 2003/09/13 05:00 [pubmed]
PHST- 2003/12/11 05:00 [medline]
PHST- 2003/09/13 05:00 [entrez]
PHST- 2006/10/01 00:00 [pmc-release]
AID - 0521448 [pii]
AID - 10.1136/gut.52.10.1448 [doi]
PST - ppublish
SO  - Gut. 2003 Oct;52(10):1448-56. doi: 10.1136/gut.52.10.1448.