Gut hormones: emerging role in immune activation and inflammation

Abstract

SummaryGut inflammation is characterized by mucosal recruitment of activated cells from both the innate and adaptive immune systems. In addition to immune cells, inflammation in the gut is associated with an alteration in enteric endocrine cells and various biologically active compounds produced by these cells. Although the change in enteric endocrine cells or their products is considered to be important in regulating gut physiology (motility and secretion), it is not clear whether the change plays any role in immune activation and in the regulation of gut inflammation. Due to the strategic location of enteric endocrine cells in gut mucosa, these gut hormones may play an important role in immune activation and promotion of inflammation in the gut. This review addresses the research on the interface between immune and endocrine systems in gastrointestinal (GI) pathophysiology, specifically in the context of two major products of enteric endocrine systems, namely serotonin (5-hydroxytryptamine: 5-HT) and chromogranins (Cgs), in relation to immune activation and generation of inflammation. The studies reviewed in this paper demonstrate that 5-HT activates the immune cells to produce proinflammatory mediators and by manipulating the 5-HT system it is possible to modulate gut inflammation. In the case of Cgs the scenario is more complex, as this hormone has been shown to play both proinflammatory and anti-inflammatory functions. It is also possible that interaction between 5-HT and Cgs may play a role in the modulation of immune and inflammatory responses. In addition to enhancing our understanding of immunoendocrine interaction in the gut, the data generated from the these studies may have implications in understanding the role of gut hormone in the pathogenesis of both GI and non-GI inflammatory diseases which may lead ultimately to improved therapeutic strategies in inflammatory disorders.

Targeted Inhibition of Serotonin Type 7 (5-HT7) Receptor Function Modulates Immune Responses and Reduces the Severity of Intestinal Inflammation

“…7G). 3 receptor antagonists, granisetron and tropisetron, were shown to protect against rat colitis and were associated with a decreased inflammatory response in the gut (49, 50). 5-HT 3 receptor antagonists may modulate 5-HT release from EC cells (which express 5-HT 3 receptors), thereby attenuating inflammation (52).…”

“…About 95% of the body's 5-HT is located in the GI tract, and enterochromaffin (EC) cells are its main source (1, 2). 5-HT is also found in enteric neurons, but the 5-HT amount present in enteric neurons appears to be very small in comparison with that present in EC cells (∼90% of 5-HT is found in EC cells and 10% in enteric neurons) (3). Tryptophan hydroxylase (TPH) catalyzes the rate-limiting step in the synthesis of 5-HT from tryptophan and has been detected prominently in EC cells (4).…”

Avaliação dos efeitos de 5-hidroxitriptofano em-hidroxibenzilhidrazine associados a Lactobacillus spp. na morfometria intestinal e imunomarcação de serotonina em frangos de corte desafiados com Salmonella Enteridis

“…Sua liberação para o lúmen ou lâmina própria faz com que atue sobre células entéricas do sistema nervoso e inicie atividades secretó-rias e crescimento celular de vários tecidos, incluindo vilosidades e criptas intestinais (Fukumoto et al 2003, Hasler 2009, Khan & Ghia 2010.…”

Chlamydiae in Gastrointestinal Disease

“…Both serotonin and CgA are important for immune activation and gut inflammation in vivo and several serotonergic receptors have been characterized in lymphocytes, monocytes, macrophages and dendritic cells (Cloez-Tayarani & Changeux, 2007). Serotonin has been shown to activate immune cells, which are responsible for the production of proinflammatory mediators (Khan & Ghia, 2010). Consequently, a manipulation of the serotonin system could modulate responses to gut inflammation.…”

“…Consequently, a manipulation of the serotonin system could modulate responses to gut inflammation. CgA on the other hand has antimicrobial activity (Shooshtarizadeh et al, 2010) and exhibits both proinflammatory and anti-inflammatory functions (Khan & Ghia, 2010).…”