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Calcitonin Gene-Related Peptide Expression in Sepsis
  1. Vivian Suarez Domenech,
  2. Eric S. Nylen,
  3. Jon C. White,
  4. Richard H. Snider Jr,
  5. Kenneth L. Becker,
  6. Regine Landmann,
  7. Beat Müller
  1. 1From the Departments of Research and Internal Medicine, University Hospitals, Basel, Switzerland (V.S.D., R.L., B.M.)
  2. 2VA Medical Center and George Washington University, Washington, DC (J.C.W., R.H.S., E.S.N., K.L.B.).
  1. Supported in part by research grants (Swiss National Foundation 32-59012.99, Sonderprogram zu Förderung des akademischen Nachwuchses der Univerität Basel, Nora van Meeuwen-Häfliger Foundation) for Beat Müller.
  2. Address all correspondence to: Beat Müller, MD, Division of Endocrinology, Diabetology, and Clinical Nutrition, Department of Internal Medicine, University Hospitals, Petersgraben 4, CH-4031 Basel, Switzerland. E-mail happymiller{at}bigfoot.com

Postulation of Microbial Infection-Specific Response Elements Within the Calcitonin I Gene Promoter

Abstract

Background Recently, we reported an unexpected ubiquitous expression of calcitonin (CT)-mRNA in a hamster peritonitis model of sepsis. Using this animal model, we undertook a study to further investigate the pattern of expression of the calcitonin I (CALC-I) gene and CT gene-related peptide (CGRP)-mRNA in sepsis.

Methods Live Escherichia coli impregnated in 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 the Taq-Man technique, and compared with the mRNA expression of CT, tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6). The 5′ untranslated regions of the mRNA and potential alternative splicing sites were identified by 5′ rapid amplification of cDNA ends.

Results We found a tissue-wide, ubiquitous and uniform expression of CGRP-mRNA in all septic tissues examined. CGRP-mRNA was detectable by RT-PCR in various extraneuronal and extrathyroidal septic tissues, but not in healthy control tissues. As found for CT-mRNA in our earlier studies, CGRP-mRNA seemed to be more specifically up-regulated as compared with other classical cytokines (ie, IL-6 and TNF-α). Importantly, the 5′ untranslated sequence in control and septic thyroid was similar to the sequence obtained from septic spleen.

Conclusions We postulate the presence of microbial infection-specific response elements in the CALC-I gene promotor, which, upon a specific stimulus, override the tissue-selective expression pattern. This new form of endocrine plasticity may be of importance in the response to systemic inflammation.

Keywords
  • calcitonin gene-related peptide
  • calcitonin gene-related peptide mRNA
  • CALC-I gene
  • sepsis
  • gene promoter
  • procalcitonin
  • calcitonin

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