Gene Expression of Transient Receptor Potential Channels in Peripheral Blood Mononuclear Cells of Inflammatory Bowel Disease Patients

Morita, Tatsushi; Mitsuyama, Keiichi; Yamasaki, Hiroshi; Mori, Atsushi; Yoshimura, Tetsuhiro; Araki, Toshihiro; Morita, Masaru; Tsuruta, Kozo; Yamasaki, Sayo; Kuwaki, Kotaro; Yoshioka, Shinichiro; Takedatsu, Hidetoshi; Torimura, Takuji

doi:10.3390/jcm9082643

Cited by 15 publications

(16 citation statements)

References 53 publications

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“…In addition, administration of CB2 agonists or PAR-2 antagonist to mice with inflammatory pain or with knee joint pain led to the reduction of NLRP3 inflammasome activation [ 37 , 38 ]. Previous studies have widely described the sensitization of these nociceptor pathways in gastrointestinal inflammation by immune mediators [ 39 , 40 , 41 , 42 ]. Specifically, our data indirectly indicate that the inflammasome pathway can also regulate the expression of these mucosal nociceptors and their subsequent effect on visceral pain.…”

Section: Discussionmentioning

confidence: 99%

Inflammasome Signaling Regulates the Microbial–Neuroimmune Axis and Visceral Pain in Mice

Aguilera

Rossini

Hickey

et al. 2021

IJMS

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Interactions between the intestinal microbiota, immune system and nervous system are essential for homeostasis in the gut. Inflammasomes contribute to innate immunity and brain–gut interactions, but their role in microbiota–neuro–immune interactions is not clear. Therefore, we investigated the effect of the inflammasome on visceral pain and local and systemic neuroimmune responses after antibiotic-induced changes to the microbiota. Wild-type (WT) and caspase-1/11 deficient (Casp1 KO) mice were orally treated for 2 weeks with an antibiotic cocktail (Abx, Bacitracin A and Neomycin), followed by quantification of representative fecal commensals (by qPCR), cecal short chain fatty acids (by HPLC), pathways implicated in the gut–neuro-immune axis (by RT-qPCR, immunofluorescence staining, and flow cytometry) in addition to capsaicin-induced visceral pain responses. Abx-treatment in WT-mice resulted in an increase in colonic macrophages, central neuro-immune interactions, colonic inflammasome and nociceptive receptor gene expression and a reduction in capsaicin-induced visceral pain. In contrast, these responses were attenuated in Abx-treated Casp1 KO mice. Collectively, the data indicate an important role for the inflammasome pathway in functional and inflammatory gastrointestinal conditions where pain and alterations in microbiota composition are prominent.

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Section: Discussionmentioning

confidence: 99%

Inflammasome Signaling Regulates the Microbial–Neuroimmune Axis and Visceral Pain in Mice

Aguilera

Rossini

Hickey

et al. 2021

IJMS

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“…Using PBMCs obtained from a different cohort of patients with IBD (Table S1 ) [ 24 ], we evaluated LRG mRNA levels in patients with IBD. Blood samples (10 mL) were obtained by cubital venous puncture and collected in standard sterile polystyrene vacuum tubes with heparin.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of Serum Leucine-Rich Alpha-2 Glycoprotein as a New Inflammatory Biomarker of Inflammatory Bowel Disease

Yoshimura

Mitsuyama

Sakemi

et al. 2021

Mediators of Inflammation

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Studies on serum leucine-rich alpha-2 glycoprotein (LRG) in inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), are scarce; the methods for estimating disease activity are less established, particularly for CD. This study is aimed at evaluating the utility of serum LRG as a potential inflammatory marker for IBD and to investigate the LRG gene expression in peripheral blood mononuclear cells (PBMCs) as a possible source of serum LRG. Overall, 98 patients with UC and 96 patients with CD were prospectively enrolled and clinically evaluated; 92 age-matched individuals served as the healthy controls. The blood samples were analyzed for serum LRG levels and routine laboratory parameters. Disease activity was assessed clinically and endoscopically. Finally, LRG gene expression in the PBMCs from a different cohort (41 patients with UC, 34 patients with CD, and 30 healthy controls) was examined. The serum LRG levels were higher during active disease than during inactive disease; additionally, serum LRG levels were positively correlated with clinical disease activity, C-reactive protein (CRP) levels, and other laboratory parameters in patients with UC and CD and with endoscopic disease activity in UC. UC and CD showed comparable areas under the curve (AUC) values for determining clinical remission and differentiating between endoscopic remission associated with LRG and CRP. The levels of LRG mRNA were also increased in PBMCs from patients with UC and CD and reflected disease activity. These data suggest that serum LRG, originated partially from PBMCs, is an inflammatory marker in UC and CD. A large-scale well-designed study should be conducted in the future to more accurately reveal the clinical significance of LRG in patients with IBD.

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“…Transient Receptor Potential Melastatin-8 (TRPM8) is a non-selective cation channel activated by cold temperature and by cooling agents, and a neuronal sensor that plays a role in cold and mechanical allodynia associated with neuropathic pain secondary to trauma. It was proved that this channel is involved in pain perception, and that TRPM8 activation or deactivation can modulate analgesia [114]. De Petrocellis demonstrated in his paper that CBG is the second most efficient TRPM8 antagonist, and he found that a "CBG-free" extract from the Cannabis plant (with the exact quantity of CBG that was extracted from the plant) was inactive per se, but when added to pure CBG, the activity of the CBG-enriched extract was significantly increased, and it was more efficient in antagonizing TRPM8 than pure CBG.…”

Section: Cannabigerol (Cbg)-type Compoundsmentioning

confidence: 99%

Major Phytocannabinoids and Their Related Compounds: Should We Only Search for Drugs That Act on Cannabinoid Receptors?

et al. 2021

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The most important discoveries in pharmacology, such as certain classes of analgesics or chemotherapeutics, started from natural extracts which have been found to have effects in traditional medicine. Cannabis, traditionally used in Asia for the treatment of pain, nausea, spasms, sleep, depression, and low appetite, is still a good candidate for the development of new compounds. If initially all attention was directed to the endocannabinoid system, recent studies suggest that many of the clinically proven effects are based on an intrinsic chain of mechanisms that do not necessarily involve only cannabinoid receptors. Recent research has shown that major phytocannabinoids and their derivatives also interact with non-cannabinoid receptors such as vanilloid receptor 1, transient receptor ankyrin 1 potential, peroxisome proliferator-activated receptor-gamma or glitazone receptor, G55 protein-coupled receptor, and nuclear receptor, producing pharmacological effects in diseases such as Alzheimer’s, epilepsy, depression, neuropathic pain, cancer, and diabetes. Nonetheless, further studies are needed to elucidate the precise mechanisms of these compounds. Structure modulation of phytocannabinoids, in order to improve pharmacological effects, should not be limited to the exploration of cannabinoid receptors, and it should target other courses of action discovered through recent research.

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Gene Expression of Transient Receptor Potential Channels in Peripheral Blood Mononuclear Cells of Inflammatory Bowel Disease Patients

Cited by 15 publications

References 53 publications

Inflammasome Signaling Regulates the Microbial–Neuroimmune Axis and Visceral Pain in Mice

Inflammasome Signaling Regulates the Microbial–Neuroimmune Axis and Visceral Pain in Mice

Evaluation of Serum Leucine-Rich Alpha-2 Glycoprotein as a New Inflammatory Biomarker of Inflammatory Bowel Disease

Major Phytocannabinoids and Their Related Compounds: Should We Only Search for Drugs That Act on Cannabinoid Receptors?

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