Endocrine Abstracts (2007) 13 S27

Corticotropin Releasing Hormone (CRH) system and inflammation

Katia Karalis1, Christina Chandras1 & Thalia Teli1


1Foundation for Biomedical research of the Academy of Athens, Papagou, Athens, Greece; 2Division of Endocrinology, Children’s Hospital, Boston, United States.


Corticotropin Releasing Hormone (CRH) is the hypothalamic mediator of the stress response that ultimately results in increased release of glucocorticoid. CRH exerts its effects by binding to the CRH receptors 1 and 2 that belong to the family of the GPCRs. As we and others have shown in rodent and human tissues, peripherally expressed CRH is a potent proinflammatory factor. The immunomodulatory effects of CRH are exerted by its activation of the NF-κB DNA binding activity in immune cells and the corresponding activation of cytokines mainly via binding to CRHR2.

The proinflammatory effects of CRH in acute inflammatory responses have been confirmed with the use of the Crh-null (Crh−/−) mice, that raise a significantly lower inflammatory response to a variety of stimuli. In our recent studies we have shown that Crh deficient mice have lower expression of the Toll-like receptor (TLR)-4 in a variety of tissues including the intestine. To evaluate the effects of the lower expression of TLR4 in Crh−/− mice in the development of an inflammatory response, we used a model of experimental ulcerative colitis induced by DSS. It has been shown that TLR4- and/or, its downstream adaptor protein, MyD88- deficiency result in increased susceptibility to DSS-induced colitis. Our findings show that Crh−/− are not protected from the development of colitis as expected by their deficiency in CRH, a proinflammatory factor with confirmed effects in intestinal inflammation. We suggest that the regulation of the TLR4 system by CRH is biologically significant, while it provides a model to investigate the contribution of the stress axis in the regulation of the innate immune system.

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