Participation of cold sensitive TRPM8 ion channel in modulation of metabolism and immune response
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Institute of Physiology Russian Academy of Medical Sciences, Thermophysiology, Russia
The response of living organism to any stimulus is a combination of the responses of various physiological systems which is determined by the regulatory afferent structures providing constant and precise interaction of the systems. Relationship of thermoregulatory and immune systems is an important aspect of unsolved problems, because the widespread influence of temperature on the body. Results of recent studies indicate that temperature-sensitive TRP ion channels are the basis of thermoreceptors which form the response to temperature. Cold-sensitive ion channel TRPM8 is most interesting because it works in the range of physiological temperatures. One of the TRPM8 agonists is menthol. Currently, more attention is attracted to physiological and pathological functions of TRP ion channels but their possible role in maintenance of body health is not clear.
In thermoneutral conditions (Fig. 1, top) activation of the cold-sensitive TRPM8 ion channel by menthol, produces a significant increase in total metabolism due to enhancement of fat oxidation. The observed shift in metabolism without any temperature changes but under the effect of TRPM8 activation suggests its continuous involvement in regulation of total metabolism and, presumably, in defining the particular type of metabolism of living organism (Kozyreva et al., 2010).
Activation of TRPM8 in thermoneutral conditions causes also changes in immune response: 1) significant increase in antigen binding in spleen and peritoneal exudate; 2) suppression of antibody formation in spleen; 3) considerable decrease in blood level of IgG (Kozyreva et al., 2012). The measurement of the blood level of interleukins (Kits ELISA) has shown that activation of TRPM8 ion channel by menthol increases the level of IL-6 and IL-1β (Fig. 2). This was quit close to changes in these cytokine levels at slow deep cooling. This allows us to suggest the participation of TRPM8 ion channel in regulation of these cytokine levels.
At cooling (Fig. 1, bottom). Agonist of cold-sensitive TRPM8 ion channel, menthol decreases the temperature thresholds of all thermoregulatory responses to cooling (heat production and heat loss). Under menthol stimulation, there was enhancement of the urgent phase of metabolic response at rapid cooling, and an increase in the skin blood vessel constrictor response at slow cooling. We have shown that shallow cooling stimulates but deep cooling inhibits the immune response. Activation of TRPM8 ion channel by menthol eliminates the inhibitory effect of subsequent deep cooling on immune response (Kozyreva et al., 2002; 2010; 2012).
Thus, activation of TRPM8 by menthol enhances the resistance of organism to cooling by better maintenance of both temperature homeostasis and the function of immune system. It can be suggested that a significant influence of TRPM8 agonist menthol on the immune response is mainly related to its peripheral effects. This is in consistent with our data (Voronova et al., 2013) on not high expression of Trpm8 gene in brain structures, and evidenced expression of this ion channel in sensory skin afferents (Dhaka et al., 2008). Elucidation of the mechanisms of TRPM8 ion channel effects requires further researches.
References
1. Voronova IP, Tuzhikova AA, and Kozyreva TV. Gene expression of thermosensitive TRP ion channels in the rat brain structures: effect of adaptation to cold. J. Thermal Biology (2013) 38(6): 300-304.
2. Dhaka A, Earley T, Watson J, and Patapoutian A. Visualizing cold spots: TRPM8-expressing sensory neurons and their projections. J. Neurocsience. (2008) 28: 566-575.
3. Kozyreva TV, Kozaruk VP, Tkachenko EYa, and Khramova GM. Agonist of TRPM8 channel, menthol, facilitates the initiation of thermoregulatory responses to external cooling. J. Thermal Biology (2010) 35(8): 428-434.
4. Kozyreva TV, Khramova GM, and Eliseeva L S. The influence of TRPM8 ion channel activation on immune response at different temperature conditions. J. Thermal Biology (2012) 37: 648-653.
5. Kozyreva T.V., Eliseeva L.S. Effects of cold exposure at various rates and depth on the response to antigen of spleen and peritoneal cells and on plasma corticosterone. In: Tochihara Y, editor. Environmental Ergonomics X. Fukuoka. (2002). p. 29-32.
Keywords:
TRPM8 ion channel,
Metabolism,
immune response,
Cold Temperature,
Interleukins
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Adaptive Immunity
Citation:
Kozyreva
TV
(2013). Participation of cold sensitive TRPM8 ion channel in modulation of metabolism and immune response.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00951
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Received:
27 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Prof. Tamara V Kozyreva, Institute of Physiology Russian Academy of Medical Sciences, Thermophysiology, Novosibirsk, Russia, Kozyreva@physiol.ru