المؤلفون: Kanauchi, Yuya, Yamamoto, Takeshi, Yoshida, Minako, Zhang, Yue, Lee, Jaemin, Hayashi, Shusaku, Kadowaki, Makoto

المصدر: Scientific Reports; 1/7/2022, Vol. 12 Issue 1, p1-18, 18p

مصطلحات موضوعية: NICOTINIC receptors, CHOLINERGIC mechanisms, INFLAMMATORY bowel diseases, DENDRITIC cells, COLITIS, NICOTINIC acetylcholine receptors, ULCERATIVE colitis

مستخلص: Ulcerative colitis (UC) is a chronic inflammatory bowel disease. Several studies have demonstrated that α7 nicotinic acetylcholine receptors (α7nAChRs) exert anti-inflammatory effects on immune cells and nicotine suppress UC onset and relapse. Plasmacytoid dendritic cells (pDCs) reportedly accumulate in the colon of UC patients. Therefore, we investigated the pathophysiological roles of α7nAChRs on pDCs in the pathology of UC using oxazolone (OXZ)-induced Th2-type colitis with BALB/c mice. 2-deoxy-D-glucose, a central vagal stimulant suppressed OXZ colitis, and nicotine also ameliorated OXZ colitis with suppressing Th2 cytokines, which was reversed by α7nAChR antagonist methyllycaconitine. Additionally, α7nAChRs were expressed on pDCs, which were located very close to cholinergic nerve fibers in the colon of OXZ mice. Furthermore, nicotine suppressed CCL21-induced bone marrow-derived pDC migration due to Rac 1 inactivation, which was reversed by methyllycaconitine, a JAK2 inhibitor AG490 or caspase-3 inhibitor AZ-10417808. CCL21 was mainly expressed in the isolated lymphoid follicles (ILFs) of the colon during OXZ colitis. The therapeutic effect of cholinergic pathway on OXZ colitis probably through α7nAChRs on pDCs were attributed to the suppression of pDC migration toward the ILFs. Therefore, the activation of α7nAChRs has innovative therapeutic potential for the treatment of UC. [ABSTRACT FROM AUTHOR]

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المؤلفون: Yamamoto, Takeshi, Zhang, Yue, Kigasawa, Ai, Hayashi, Shusaku, Kadowaki, Makoto

المصدر: Evidence-based Complementary & Alternative Medicine (eCAM); 10/23/2020, p1-10, 10p, 3 Charts, 7 Graphs

مصطلحات موضوعية: ANIMAL experimentation, ATOPIC dermatitis, CELL motility, CHEMOKINES, CONTACT dermatitis, DENDRITIC cells, GINSENG, IMMUNITY, LIGANDS (Biochemistry), MEDICINAL plants, ASIAN medicine, MICE, ORAL drug administration, PLANT extracts

مستخلص: Dendritic cells (DCs) are well known to be essential immunocytes involved in innate and adaptive immunity. DCs are classified as conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs). Recently, the accumulation of pDCs in inflamed tissues and lymphoid tissues has been considered to be a possible contributing factor in the development of immunological diseases, but little is known about the pathophysiological roles of pDCs in immunological diseases. To date, many studies have demonstrated that many kinds of Kampo formulas can regulate immunological reactions in human immune diseases. Thus, we screened Kampo formulas to identify an agent that inhibits pDC migration. Furthermore, we investigated the therapeutic effects of these formulas on a murine DNFB-induced allergic contact dermatitis model. Bone marrow-derived pDCs (BMpDCs) were derived from the bone marrow cells of BALB/c mice in a culture medium with Flt3 ligand. The effects of Kampo formulas on BMpDC migration were evaluated by assessing the number, velocity, and directionality of BMpDCs chemotaxing toward the more concentrated side of a chemokine (C-C motif) ligand 21 (CCL21) gradient. The Kampo formulas that exerted inhibitory effects on pDC migration were orally administered to DNFB-induced allergic contact dermatitis model mice. Byakkokaninjinto reduced the number of migrated BMpDCs and suppressed the velocity and directionality of BMpDC migration in a chemotaxis assay. Gypsum Fibrosum and Ginseng Radix, which are components of byakkokaninjinto, obviously suppressed the velocity of BMpDC migration. Furthermore, Gypsum Fibrosum significantly suppressed the directionality of BMpDC migration. In DNFB-induced allergic contact dermatitis model mice, byakkokaninjinto markedly abrogated ear swelling in late-phase allergic reactions. In conclusions, byakkokaninjinto, which has an inhibitory effect on pDC migration, was able to prevent the occurrence of allergic contact dermatitis, suggesting that pDCs were involved in the onset of allergic contact dermatitis in the mouse model. Therefore, byakkokaninjinto is anticipated to be a therapeutic agent for disorders related to pDC migration. [ABSTRACT FROM AUTHOR]

: Copyright of Evidence-based Complementary & Alternative Medicine (eCAM) is the property of Hindawi Limited and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Zhang, Yue¹ (AUTHOR), Yamamoto, Takeshi¹ (AUTHOR) ty@inm.u-toyama.ac.jp, Hayashi, Shusaku¹ (AUTHOR), Kadowaki, Makoto¹ (AUTHOR)

المصدر: Biomedicine & Pharmacotherapy. Sep2021, Vol. 141, pN.PAG-N.PAG. 1p.

مصطلحات موضوعية: *DENDRITIC cells, *COLITIS, *CELL migration, *INFLAMMATORY bowel diseases, *THERAPEUTICS

مستخلص: Dendritic cells (DCs) play a pivotal role in maintaining immunological homeostasis by orchestrating innate and adaptive immune responses via migration to inflamed sites and the lymph nodes (LNs). Plasmacytoid DCs (pDCs) have been reported to accumulate in the colon of inflammatory bowel disease (IBD) patients and dextran sulfate sodium (DSS)-induced colitis mice. However, the role of pDCs in the progression of colonic inflammation remains unclear. 80 compounds in natural medicines were searched for inhibitors of pDC migration using bone marrow-derived pDCs (BMpDCs) and conventional DCs (BMcDCs). BALB/c mice were given 3% DSS in the drinking water to induce acute colitis. Compounds, which specifically inhibited pDC migration, were administrated into DSS-induced colitis mice. Astragaloside IV (As-IV) and oxymatrine (Oxy) suppressed BMpDC migration but not BMcDC migration. In DSS-induced colitis mice, the number of pDCs was markedly increased in the colonic lamina propria (LP), and the expression of CCL21 was obviously observed in colonic isolated lymphoid follicles (ILFs). As-IV and Oxy reduced symptoms of colitis and the accumulation of pDCs in colonic ILFs but not in the colonic LP. Moreover, in a BMpDC adoptive transfer model, BMpDC migration to colonic ILFs was significantly decreased by treatment with As-IV or Oxy. pDCs accumulated in the colon of colitis mice, and As-IV and Oxy ameliorated colitis by suppressing pDC migration to colonic ILFs. Accordingly, the selective inhibition of pDC migration may be a potential therapeutic approach for treating colonic inflammatory diseases. [ABSTRACT FROM AUTHOR]

المؤلفون: Yamamoto, Takeshi¹ (AUTHOR) ty@inm.u-toyama.ac.jp, Matsunami, Emi¹ (AUTHOR), Komori, Koji¹ (AUTHOR), Hayashi, Shusaku¹ (AUTHOR), Kadowaki, Makoto¹ (AUTHOR)

المصدر: Biochemical & Biophysical Research Communications. Aug2019, Vol. 516 Issue 3, p626-631. 6p.

مصطلحات موضوعية: *IMMUNOLOGICAL tolerance, *FOOD allergy, *T cells, *DENDRITIC cells, *TRETINOIN, JAPANESE herbal medicine

مستخلص: The disruption of intestinal mucosal immune tolerance can lead to the development of intestinal immune diseases such as food allergy (FA). Regulatory T cells (Tregs) in the mucosa play a critical role in maintaining peripheral immune tolerance in the intestine, and retinoic acid (RA) is absolutely required for the induction of Tregs. We have previously reported that kakkonto, a traditional Japanese herbal medicine, suppresses FA in a murine FA model due to the induction of Tregs in the colonic mucosa. However, the precise molecular mechanisms underlying the induction of Tregs remain unclear. Puerarin, an isoflavone derivative, is a major constituent of kakkonto. Thus, we investigated the effect of puerarin on the induction of Tregs. BALB/c mice were systemically sensitized and then orally challenged with ovalbumin (OVA) as an FA model. Puerarin treatment suppressed the development of allergic diarrhea in FA mice. The gene expression levels of IL-4 and mast cell protease I (mMCP-1) were significantly upregulated in the proximal colon of FA mice but were reduced by puerarin. The proportions of Foxp3+CD4+ cells and CD103+CD11c+ dendritic cells (DCs) were significantly higher among the colonic lamina propria (cLP) cells of puerarin-treated FA mice than among those of untreated FA mice. The gene expression of Aldh1a1, an RA synthesis enzyme, in colonic epithelial cells (CECs) was significantly higher in the puerarin-treated FA mouse colon than in the untreated FA mouse colon. In addition, the preventive effect of puerarin was suppressed in the FA model by pretreatment with LE540, an RA receptor (RAR) antagonist. The induction of Foxp3+CD4+ cells and CD103+CD11c+ DCs by puerarin was reduced by pretreatment with LE540. The present findings indicate that the augmentation of RA production in CECs induced by puerarin enhances the induction of Tregs and suppresses the development of FA in a mouse model. Thus, a natural enhancer of RA production, such as puerarin, has the potential to treat immune diseases attributed to Treg deficiency. • Puerarin suppressed the development of allergic diarrhea in FA mice. • Puerarin induced Foxp3+ Tregs and CD103+ DCs in the colon of FA mice. • Effect of puerarin was suppressed by pretreatment with an RA receptor antagonist. • Puerarin upregulated the Aldh1a1 mRNA expression in the colonic epithelial cells. • Augmentation of RA production induced by puerarin suppresses the development of FA. [ABSTRACT FROM AUTHOR]