A study published in PLoS One indicates the presence of distinctive interactions between neurotensin (NT), corticotropin-releasing hormone (CRH) and mast cells that may be involved in inflammatory- and/or stress-related diseases.
Psychological stress is known to aggravate asthma, migraines and certain autoimmune/inflammatory diseases. Although the mechanisms of stress-induced exacerbations of these conditions are not fully understood, several studies indicate that mast cells may play an important role in this process.
Mast cells are found in many body’s tissues, typically associated with blood vessels. In several organs, including the lymphoid tissue, a close spatial relationship between peptidergic nerve fibers and mast cells, T cells and macrophages is often observed.
The close juxtaposition of mast cells clusters to nerve fibers may contribute to their stimulation by neuropeptides and neurotransmitters as well as by acute psychological stress.
Neuropeptides such as peripheral CRH and substance P (SP) are potent mast cell secretagogues. Thus, acute stress might induce pro-inflammatory activities in certain tissues through neural activation of the peripheral CRH/SP–mast cell–histamine axis.
Recently, neurotensin (NT), a vasoactive 13-amino acid peptide, identified and isolated in the 1970s (for short overview and its actions, see our previous news report), has been implicated in this process. Previous research indicates that neurotensin is involved in the skin mast cell degranulation induced by immobilization stress. The neuropeptide also increases vascular permeability through mast cell activation. Mast cells express neurotensin receptors (NTRs) and their stimulation results in histamine release, whereas intravenous injection of neurotensin increases the level of blood histamine.
In the PLoS One study, Konstantinos–Dionysios Alysandratos and colleagues from the Department of Molecular Physiology and Pharmacology, Tufts University School of Medicine, Boston, Massachusetts, demonstrate that neurotensin triggers human mast cell degranulation, stimulates human mast cells to release vascular endothelial growth factor (VEGF) and augments the effect of CRH on VEGF release through a NTR specific manner.
The study also indicates the involvement of NF-kB activation in this process, and that neurotensin induces CRHR-1 expression and CRH can induce NTR expression on mast cells. Previous studies have also indicated that NTR activation leads to release of IL-8 and TNF, which can further promote inflammation.
The authors suggest that the interactions between neurotensin and CRH, resulting in mast cells activation and degranulation might influence the onset and/or course of autoimmune/inflammatory or allergic diseases.