scholarly journals Topical Application of Doxycycline Inhibits Th2 Cell Development Mediated by Langerhans Cells and Exerts a Therapeutic Effect on Atopic Dermatitis

2020 ◽  
Vol 23 ◽  
pp. 86-99 ◽  
Author(s):  
Katsuhiko Matsui ◽  
Yuki Nojima ◽  
Yuka Kajiwara ◽  
Kana Busujima ◽  
Yuki Mori
Keyword(s):  
Atopic Dermatitis ◽  
Lymph Nodes ◽  
Topical Application ◽  
Severity Score ◽  
Langerhans Cells ◽  
Skin Lesions ◽  
Cell Development ◽  
Th2 Cells ◽  
Th2 Cytokines ◽  
Th2 Cell

Background: Langerhans cells (LCs) polarize the immune milieu towards a T helper type (Th) 1 or Th2 immune response. We investigated the effects of selected tetracyclines on Th cells development mediated by LCs, and their implications for the treatment of atopic dermatitis (AD). Methods: Mice were primed with ovalbumin (OVA) peptide-pulsed LCs, which had been treated with each antibiotic, via the hind footpad. After 5 days, the Th1/Th2 cytokine response in the popliteal lymph nodes was investigated by enzyme-linked immunosorbent assay. The expression of cell surface molecules on LCs was investigated using reverse transcriptase polymerase chain reaction. The therapeutic effects of a selected antibiotic on AD-like skin lesions of NC/Nga mice were assessed in terms of the skin severity score, histological changes in the lesioned skin, the serum level of total IgE, and expression of Th1/Th2 cytokines in lymph nodes and skin lesions. Results: Antibiotic-treated, OVA peptide-pulsed LCs inhibited development of Th2 cells but not Th1 cells. This was accompanied by suppression of T-cell immunoglobulin and mucin domain-containing protein (TIM)-4 expression in LCs. Doxycycline had the greatest activity against Staphylococcus aureus strains isolated from skin lesions of patients with AD, and a strong inhibitory effect on Th2 cell development. Doxycycline suppressed the increase in the skin severity score during the acute phase in NC/Nga mice similar to betamethasone. This suppressive effect was associated with a decrease in the serum IgE level and production of Th2 cytokines in auricular lymph node cells and skin lesions. Conclusion: Topical application of doxycycline to AD lesions would act on both superficial S. aureus colonization and epidermal LCs, thus possibly inhibiting the development of Th2 cells in vivo, with benefits for control of acute inflammation in AD.

scholarly journals Effects of anti-allergy drugs on Th1 cell and Th2 cell development mediated by Langerhans cells

2020 ◽  
Vol 23 ◽  
pp. 412-421
Author(s):  
Katsuhiko Matsui ◽  
Xiaolei Shi ◽  
Sayuko Komori ◽  
Atsumi Higuchi
Keyword(s):  
Topical Application ◽  
Langerhans Cells ◽  
Skin Lesions ◽  
Cell Development ◽  
Enzyme Linked Immunosorbent Assay ◽  
T Helper ◽  
Down Regulation ◽  
Th1 Cell ◽  
Th2 Cell ◽  
Helper Type

Background: It is well known that Langerhans cells (LCs) work as the primary orchestrators in polarization towards T helper type 1 (Th1) or T helper type 2 (Th2) immune responses. In this study, we examined the effects of various anti-allergy drugs against the Th2 cell development by LCs. Methods: The expression of cell surface molecules on LCs was investigated using reverse transcriptase polymerase chain reaction. The effects of anti-allergy drugs on T-cell immunoglobulin and mucin domain-containing protein (TIM)-4 expression in LCs were examined to predict whether they would inhibit Th2 cell development. Next, mice were primed via the hind footpad with ovalbumin (OVA)-pulsed LCs that had been treated with selected anti-allergy drugs. After 5 days, the cytokine response in the popliteal lymph nodes was investigated by enzyme-linked immunosorbent assay. The therapeutic effects of a selected drug on atopic dermatitis (AD) were assessed using AD-like skin lesions of NC/Nga mice. Results: The first-generation histamine H1 receptorantagonists, cyproheptadine and promethazine, and the second-generation histamine H1 receptor antagonists, emedastine and loratadine, were selected as candidate inhibitors of Th2 cell development. As expected, OVA peptide-pulsed LCs that had been treated with each drug and injected into the hind footpads of mice inhibited Th2 cell development, as represented by down-regulation of interleukin (IL)-4 production. Furthermore, the LCs that had been treated withemedastine also inhibited Th1 cell development, as represented by down-regulation of interferon (IFN)-g production. This additional inhibition of Th1 cell development was accompanied by suppression of CD40 expression in LCs. Therefore, the therapeutic effect of emedastine on AD was examined. Topical application of emedastine significantly suppressed the increase in the skin severity score in NC/Nga mice with AD-like skin lesions. This suppressive effect was associated with a decrease in the production of IFN-g and IL-4 in auricular lymph node cells. Conclusions: These results suggest that topical application of emedastine to skin lesions of patients with AD may provide clinical benefits through the inhibition of both Th1 cell and Th2 cell development mediated by LCs.

scholarly journals Topical Application of Josamycin Inhibits Development of Atopic Dermatitis-Like Skin Lesions in NC/Nga Mice

2017 ◽  
Vol 20 ◽  
pp. 38 ◽  
Author(s):  
Katsuhiko Matsui ◽  
Kanta Tachioka ◽  
Kei Onodera ◽  
Reiko Ikeda
Keyword(s):  
Atopic Dermatitis ◽  
Topical Application ◽  
Serum Levels ◽  
Skin Lesions ◽  
Th2 Cells ◽  
Therapeutic Effects ◽  
Severity Scores ◽  
Superficial Skin ◽  
Ifn Γ ◽  
Th1 And Th2

Background: Patients with atopic dermatitis (AD) have superficial skin colonization by Staphylococcus aureus and an increased number of T helper type 2 (Th2) cells in their peripheral blood. Our previous study showed that josamycin, a macrolide antibiotic, had excellent bactericidal activity against S. aureus strains isolated from AD patients and simultaneously inhibited Th1 and Th2 cell development mediated by Langerhans cells. The purpose of the present study was to evaluate the effect of topical application of josamycin on AD-like skin lesions in NC/Nga mice. Methods: Josamycin (0.1%) was topically administered to NC/Nga mice with AD-like skin lesions induced by 2, 4, 6-trinitrochlorobenzene (TNCB). The therapeutic effects of josamycin were assessed by measurement of the skin severity scores, histological changes in the lesioned skin, serum levels of total IgE, and expression of interferon (IFN)-γ and interleukin (IL)-4 in lymph nodes and skin lesions. Results: Topical treatment with josamycin significantly suppressed the increase in the skin severity score in NC/Nga mice. This suppressive effect was equal to that of betamethasone, and was associated with a decrease in the density of cellular infiltration into the dermis, the mast cell count in the dermis and the serum IgE level. Furthermore, topical application of josamycin reduced the expression of IFN-γ and IL-4 in auricular lymph node cells and the skin lesions. Conclusion: The present results show that topical application of josamycin inhibits the development of AD-like skin lesions in NC/Nga mice. This suggests that topical application of josamycin to AD lesions colonized by S. aureus would be beneficial for control of AD by acting on superficially located S. aureus and by inhibiting the development of Th1 and Th2 cells.This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Norfloxacin, a Fluoroquinolone Antibiotic, Inhibits Langerhans Cell-Mediated Th1 and Th2 Cell Development

2019 ◽  
Vol 22 ◽  
pp. 122-130 ◽  
Author(s):  
Katsuhiko Matsui ◽  
Azusa Kashima ◽  
Ayaka Motegi
Keyword(s):  
Topical Application ◽  
Skin Lesions ◽  
Cell Development ◽  
T Helper ◽  
Down Regulation ◽  
Th1 Cell ◽  
Th2 Cell ◽  
Fluoroquinolone Antibiotic ◽  
Th1 And Th2 ◽  
Helper Type

Background: It is widely acknowledged that Langerhans cells (LCs) play a primary role in the polarization of T helper type 1 (Th1) or T helper type 2 (Th2) immune responses. Our aim was to find fluoroquinolone (“new quinolone”) antibiotics that would inhibit LC-mediated Th2 cell development. Methods: Expression of LC surface molecules was investigated using the reverse transcriptase polymerase chain reaction. The effects of fluoroquinolone antibiotics on T-cell immunoglobulin and mucin domain-containing protein (TIM)-4 expression in LCs were examined to predict whether they would inhibit Th2 cell development. Mice were primed via the hind footpad with ovalbumin (OVA) peptide-pulsed LCs that had been treated with a selected fluoroquinolone antibiotic, then 5 days later the cytokine response in popliteal lymph nodes was examined by enzyme-linked immunosorbent assay. Results: Norfloxacin was selected as a candidate inhibitor of Th2 cell development. As expected, OVA peptide-pulsed LCs that had been treated with norfloxacin and injected into the hind footpads of mice inhibited Th2 cell development, as represented by down-regulation of interleukin (IL)-4 production, as well as Th1 cell development, as represented by down-regulation of interferon (IFN)- g production. This additional inhibition of Th1 cell development was accompanied by suppression of CD40 expression in LCs. In addition, Staphylococcus aureus strains isolated from skin lesions of patients with atopic dermatitis (AD) were more susceptible to norfloxacin than to gentamicin. Topical treatment with norfloxacin significantly suppressed the increase in the skin severity score in NC/Nga mice with AD-like skin lesions. This suppressive effect was associated with a decrease in the production of IFN-g and IL-4 in auricular lymph node cells. Conclusions: The present results show that topical application of norfloxacin inhibits the development of AD-like skin lesions in NC/Nga mice. This suggests that topical application of norfloxacin to AD lesions colonized with S. aureus would act on both superficial S. aureus and epidermal LCs, thus possibly inhibiting the development of Th1 and Th2 cells in vivo, and controlling the severity of AD.

scholarly journals IL-27 Suppresses Th2 Cell Development and Th2 Cytokines Production from Polarized Th2 Cells: A Novel Therapeutic Way for Th2-Mediated Allergic Inflammation

2007 ◽  
Vol 179 (7) ◽  
pp. 4415-4423 ◽  
Author(s):  
Tomohiro Yoshimoto ◽  
Takayuki Yoshimoto ◽  
Koubun Yasuda ◽  
Junichiro Mizuguchi ◽  
Kenji Nakanishi
Keyword(s):  
Allergic Inflammation ◽  
Cell Development ◽  
Th2 Cells ◽  
Th2 Cytokines ◽  
Th2 Cell ◽  
Novel Therapeutic

scholarly journals Effects of Macrolide Antibiotics on Th1 Cell and Th2 Cell Development Mediated by Langerhans Cells

2016 ◽  
Vol 19 (3) ◽  
pp. 357 ◽  
Author(s):  
Katsuhiko Matsui ◽  
Saki Tamai ◽  
Reiko Ikeda
Keyword(s):  
Langerhans Cells ◽  
Cell Development ◽  
Th2 Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Macrolide Antibiotics ◽  
Mouse Bone Marrow ◽  
Down Regulation ◽  
Th1 Cell ◽  
Th2 Cell ◽  
Th2 Immune Response

ABSTRACT - Background: It is well known that Langerhans cells (LCs) work as the primary orchestrators in the polarization of the immune milieu towards a T helper type 1 (Th1) or a Th2 immune response. In this study, we investigated the effects of macrolide antibiotics on Th1 cell and Th2 cell development mediated by LCs. Methods: LC-like dendritic cells (LDCs) were generated from mouse bone marrow cells and used as substitutes for LCs. Mice were primed with ovalbumin (OVA) peptide-pulsed LDCs, which had been treated with each macrolide antibiotic, via the hind footpad. After 5 days, the cytokine response in the popliteal lymph nodes was investigated by enzyme-linked immunosorbent assay. The expression of cell surface molecules on LDCs was investigated using reverse transcriptase polymerase chain reaction. Results: Injection of OVA peptide-pulsed LDCs, which had been treated with josamycin or spiramycin, inhibited Th2 cell development as represented by down-regulation of interleukin (IL)-4 production as well as Th1 cell development as represented by down-regulation of interferon (IFN)-g production. This inhibition of Th1 cell and Th2 cell development was associated with suppression of CD86 and T-cell immunoglobulin and mucin domain-containing protein (TIM)-4 expression, respectively, in LDCs. Furthermore, Staphylococcus aureus strains isolated from skin lesions of patients with atopic dermatitis (AD) were more susceptible to josamycin than to spiramycin. Conclusions:  These results suggest that topical application of josamycin to AD lesions colonized with S. aureus would be beneficial for control of AD by acting on both superficial S. aureus and epidermal LCs, and inhibiting the development of Th2 cells.

scholarly journals IL-27 suppresses Th2 cell development and Th2 cytokines production from polarized Th2 cells: a novel therapeutic way for Th2-mediated allergic inflammation.

2010 ◽  
Vol 184 (6) ◽  
pp. 3298-3298
Author(s):  
Tomohiro Yoshimoto ◽  
Takayuki Yoshimoto ◽  
Koubun Yasuda ◽  
Junichiro Mizuguchi ◽  
Kenji Nakanishi
Keyword(s):  
Allergic Inflammation ◽  
Cell Development ◽  
Th2 Cells ◽  
Th2 Cytokines ◽  
Th2 Cell ◽  
Novel Therapeutic

scholarly journals Topical Application of Eupatilin Ameliorates Atopic Dermatitis-Like Skin Lesions in NC/Nga Mice

2017 ◽  
Vol 29 (1) ◽  
pp. 61 ◽  
Author(s):  
Ji Hyun Lee ◽  
Ye Jin Lee ◽  
Jun Young Lee ◽  
Young Min Park
Keyword(s):  
Atopic Dermatitis ◽  
Topical Application ◽  
Skin Lesions

scholarly journals Therapeutic Effects of Chinese Herbal Formula (PTQX) on NC/Nga Mice with Atopic Dermatitis-Like Skin Lesions

2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Fenggen Yan ◽  
Jing Zhang ◽  
Xiong Li ◽  
Xiumei Mo ◽  
Junfeng Liu ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Mast Cells ◽  
Lymph Nodes ◽  
Immunoglobulin E ◽  
Skin Lesions ◽  
Therapeutic Effects ◽  
Herbal Formula ◽  
Dorsal Skin ◽  
Chinese Herbal Formula ◽  
Chinese Herbal

Atopic dermatitis (AD), also known as atopic eczema, is a chronic pruritic inflammatory skin disease. The available systemic therapies for atopic dermatitis are inadequate. Objective. This study aimed to evaluate the effects of the Chinese herbal formula Pei Tu Qing Xin (PTQX) on dermatitis severity and ear swelling, immunomodulation, and the infiltration of mast cells in a mouse model of 1-chloro-2,4-dinitrobenzene- (DNCB-) induced AD. Methods. AD-like symptoms were induced by DNCB in NC/Nga mice. Skin lesions, dermatitis, ear swelling, and scratching behaviour were evaluated. Changes in the T-helper type 1 (Th1), Th2, Th17, and regulatory T (Treg) subtypes and immunoregulation in the spleen and lymph nodes were detected by flow cytometry. Results. Histopathological and immunohistochemical analyses demonstrated that PTQX decreased the DNCB-mediated induction of mast cells and infiltration of inflammatory cells in the ear and dorsal skin. PTQX also reduced the DNCB-induced increase in the serum immunoglobulin E level, pruritus, and dermatitis (red, flaky areas) on the dorsal skin. Furthermore, PTQX regulated the balance between the populations of Th1, Th2, Th17, and Treg cells (particularly the latter two) in the lymph nodes. Conclusions. Our results suggest that the Chinese herbal formula PTQX can alleviate symptoms of AD, such as epithelial damage, redness, swelling, and pruritus, and potentially be used to treat this condition.

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