MULLER B, BECKER KL, WAGNER K, NYLEN ES, SNIDER RH, HUSSAIN M, WHITE JC, HABENER JF; Interscience Conference on Antimicrobial Agents and Chemotherapy.
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2000 Sep 17-20; 40: 63.
Dept. of Internal Med., Univ. Hosp., Basel, Switzerland
BACKGROUND: In the absence of infection the CALC-I-gene is expressed in two splice forms resulting in the tissue-specific production of calcitonin and calcitonin gene related peptide (CGRP), respectively. In the classical neuroendocrine view the expression of CGRP-mRNA is restricted to some neuronal cells, whereas calcitonin (CT)-mRNA expression is restricted to C-cells of the thyroid. In humans, CGRP is the most potent vasodilator known and circulating CGRP levels were found several fold elevated in microbial infection. Recently, we reported an unexpected ubiquitous expression of CT-mRNA in a hamster peritonitis model not unlike human sepsis. Using this animal model, we undertook a study to investigate expression pattern of CGRP in sepsis.METHODS: Live Escherichia coli impregnated agar pellets were implanted in the peritoneal cavities of hamsters. Twelve hours after sepsis induction, the septic and healthy control animals were sacrificed and tissues and peritoneal macrophages were collected. CGRP-mRNA content was evaluated by reverse transcription-polymerase chain reaction (RT-PCR), quantitated by Taq-Man technique and compared to the mRNA expression of CT, TNFa, and IL6.RESULTS: We found an ubiquitous and uniform expression of CGRP-mRNA in all septic tissues examined throughout the body. CT- and CGRP-mRNA was detectable by RT-PCR in various extra-neuronal and extra-thyroidal septic tissues, but not in healthy control tissues. CGRP-mRNA appeared to be more specifically up-regulated as compared to other classical cytokines, namely IL-6 and TNFa. Conclusion: The increase of CGRP in sepsis is due to an expression of the CALC-I gene in various extrathyroidal and extraneuronal tissues and cell types throughout the body. Thereby, CGRP-mRNA appears to be more specifically up-regulated in sepsis, as compared to classical cytokines. Our data indicate that the transcriptional activation and splicing of the CALC-I-gene appears to be stimulus-specific, rather than tissue-specific. From the neuroendocrine perspective our findings are remarkable, since they challenge the paradigm of a tissue-specific transcription and splicing of the CALC-I-gene.KEYWORDS: Calcitonin; CGRP; Sepsis
Publication Types:
Keywords:
- Animals
- Calcitonin
- Calcitonin Gene-Related Peptide
- Cricetinae
- DNA, Complementary
- Gene Expression
- Humans
- Male
- RNA Splicing
- RNA, Messenger
- Reverse Transcriptase Polymerase Chain Reaction
- S100 Proteins
- S100A12 protein, human
- Sepsis
- Thyroid Gland
- Transcription, Genetic
- Vasodilator Agents
- genetics
Other ID:
UI: 102248003
From Meeting Abstracts