The Therapeutic Effect of Interleukin‐12 or Its Antagonist in Transplantation Immunity

Nishimura, Takashi; Sadata, Akiko; Yahagi, Chie; Santa, Kazuki; Otsuki, Kenzo; Watanabe, Kazuhito; Yahata, Takashi; Habu, Sonoko

doi:10.1111/j.1749-6632.1996.tb52696.x

Cited by 12 publications

(7 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…On the other hand, IL-12 promotes development of Th1-mediated immune responses. Overproduction of Th1 cytokines such as IL-12 has been implicated in the development of tissue injury in certain autoimmune and inflammatory diseases [29,30,31,32,33,34,35]. In this manner, the activation of TLR2 on monocytes and other TLRs as well as other inflammatory cells is likely involved in the pathogenesis of acne.…”

Section: Discussionmentioning

confidence: 99%

Review of the Innate Immune Response in Acne vulgaris: Activation of Toll-Like Receptor 2 in Acne Triggers Inflammatory Cytokine Responses

2005

View full text Add to dashboard Cite

Acne vulgaris is a common disorder that affects 40–50 million people in the USA alone. The pathogenesis of acne is multifactorial, including hormonal, microbiological and immunological mechanisms. One of the factors that contributes to the pathogenesis of acne is Propionibacterium acnes; yet, the molecular mechanism by which P. acnes induces inflammation is not known. Recent studies have demonstrated that microbial agents trigger cytokine responses via Toll-like receptors (TLRs). TLRs are pattern recognition receptors that recognize pathogen-associated molecular patterns conserved among microorganisms and elicit immune responses. We investigated whether TLR2 mediates P. acnes-induced cytokine production in acne. Using transfectant cells we found that TLR2 was sufficient for NF-ĸB activation in response to P. acnes. In addition, peritoneal macrophages from wild-type, TLR6 knockout and TLR1 knockout mice, but not TLR2 knockout mice, produced IL-6 in response to P. acnes.P. acnes induced activation of IL-12 and IL-8 production by primary human monocytes, and this cytokine production was inhibited by anti-TLR2-blocking antibody. Finally, in acne lesions, TLR2 was expressed on the cell surface of macrophages surrounding pilosebaceous follicles. These data suggest that P. acnes triggers inflammatory cytokine responses in acne by activation of TLR2. As such, TLR2 may provide a novel target for the treatment of this common skin disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Review of the Innate Immune Response in Acne vulgaris: Activation of Toll-Like Receptor 2 in Acne Triggers Inflammatory Cytokine Responses

2005

View full text Add to dashboard Cite

show abstract

“…Type-1 immunity is important for protecting infectious diseases and tumor. However, too much acceleration of type-1 immunity causes the onset of Th1-dependent immune diseases such as psoriasis, diabetes, graft versus host disease (GVHD) and arteriosclerosis (6,14,15,26). Therefore, it is speculated that VitD3 derivatives may be useful for the therapy of Th1-dependent immune diseases.…”

Section: Discussionmentioning

confidence: 99%

Immunomodulating effect of vitamin D3 derivatives on type-1 cellular immunity

et al. 2006

Self Cite

View full text Add to dashboard Cite

ABSTRACT1α,25-dihydroxyvitamin D3 [Calcitriol or 1,25(OH) 2 D 3 ] is an important active metabolite involved in multiple functions but its calcemic effect in vivo limits its therapeutic applications. On the other hand, 22-oxa-1α,25-dihydroxyvitamin D 3 (22-oxacalcitriol or 22-Oxa-1α,25-D 3 ), a low calcemic analog of vitamin D3 (VitD3), has been widely used as a drug for the secondary hyperparathyroidism. Here, we investigated immunomodulating effect of these two VitD3 derivatives on the differentiation of type-1 immunoregulatory cells such as dendritic cells (DC1), cytotoxic T cells (Tc1) and helper T cells (Th1). BALB/c mouse bone marrow-derived DC (BMDC1) induced by culture with Th1 condition (GM-CSF, IL-3, IL-12 and IFN-γ) expressed higher levels of MHC Class I and Class II molecules and co-stimulatory molecules compared with BMDC0 induced by neutral condition (GM-CSF + IL-3). In addition, BMDC1 showed stronger immunostimulating activity to induce alloantigen (H-2 d )-specific cytotoxic T lymphocytes (CTL) compared with BMDC0. However, if VitD3 derivatives were added into the culture for BMDC1 induction, the expression of functional molecules and type-1 IFNs were greatly inhibited. Moreover, VitD3 derivative-treated BMDC1 lost their immunostimulating activity to induce alloantigen-specific IFN-γ-producing Tc1. In addition, it was demonstrated that the addition of VitD3 derivatives inhibited the differentiation of IFN-γ-producing Th1 cells from ovalbumin (OVA)-specific naive Th cells, while it rather augmented the differentiation of IL-4-or IL-10-producing Th2 cells. There was no significant difference in immunomodulating activity between 1,25(OH) 2 D 3 and 22-Oxa-1α,25-D 3 . Thus, VitD3 derivatives are demonstrated to inhibit the functional differentiation of DC1, Tc1 and Th1 cells, which play a critical role in type-1 cellular immune responses.

show abstract

“…It has been reported that the balance between Th1 and Th2 is finally controlled by cytokines (Bogdan et al, 1991;Tanaka et al, 1996;Nishimura et al, 1996). It seems certain that IL-10 and IL-12 produced by macrophages of antigen-presenting cells have a strong influence on differentiation to Th1 and Th2 (Szabo et al, 1997;Howard and O'Garra, 1992;Mosmann and Moore, 1991).…”

Section: Discussionmentioning

confidence: 99%