Th1 and Th2 cytokines differentially regulate the transformation of Kupffer cells into multinucleated giant cells but similarly enhance the Kupffer cell-induced hepatic stellate cell proliferation

Atsukawa, Kazuhiro; Saito, Hidetsugu; Tsukada, Nobuhiro; Akiba, Yasutada; Toda, Kyoko; Kumagai, Naoya; Ohishi, Tazuko; Kamegaya, Yoshitaka; Ishii, Hiromasa

doi:10.1016/s1386-6346(00)00133-9

Cited by 3 publications

(1 citation statement)

References 27 publications

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“…(17,18) Our previous studies (19,20) demonstrating the differential effects of Th1 and Th2 cytokines on hepatic inflammation through hepatic residual macrophage Kupffer cells also support that the Th1/Th2 balance plays a crucial role in chronic hepatitis. Thus, genetically determined and differentially expressed IRF-1, which is important to the Th1-type immune response, may restrict an individual inflammatory response in the liver.…”

Section: Injection Of Ifn-bmentioning

confidence: 78%

The Detection of IRF-1 Promoter Polymorphisms and Their Possible Contribution to T Helper 1 Response in Chronic Hepatitis C

Saito

Tada²,

Wakabayashi³

et al. 2002

Journal of Interferon & Cytokine Research

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We described the interferon (IFN) regulatory factor-1 (IRF-1) promoter single nucleotide polymorphisms (SNPs), and the clinical and immunologic implications of these SNPs have been investigated. We successfully determined the mutation at -300 of the IRF-1 promoter by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and this mutation linked with other mutations in the promoter region. In our Japanese population, the frequency of the type -300*A/A was 11.9%, type A/G was 54.2%, and type G/G was 33.9%. We found no significant difference without IFN stimulation in the production levels of IFN-gamma and interleukin-10 (IL-10) from peripheral blood mononuclear cells (PBMC) between subjects with -300*A/A and those with other types. IFN-alpha stimulation, however, increased the levels of IFN-gamma significantly and decreased the IL-10 production level significantly only in the subject with -300*A/A type. Flow cytometric analysis showed that the Th1-type CD4(+) cell population was significantly increased by IFN-beta administration only in the patient with chronic hepatitis C with -300*A/A type. These results suggest that the IRF-1 promoter SNP types are positively involved in Th1-type response and, consequently, the -300*A/A type may be beneficial for viral elimination in chronic hepatitis C and IFN therapy.

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Section: Injection Of Ifn-bmentioning

confidence: 78%

The Detection of IRF-1 Promoter Polymorphisms and Their Possible Contribution to T Helper 1 Response in Chronic Hepatitis C

Saito

Tada²,

Wakabayashi³

et al. 2002

Journal of Interferon & Cytokine Research

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Relationship between serum cytokine levels and histopathological changes of liver in patients with hepatitis B

Akpolat¹,

Yahşi²,

Gödekmerdan³

et al. 2005

WJG

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Application of TGF‑β1, TIMP‑1 and TIMP‑2 small interfering RNAs can alleviate CCl₄‑induced hepatic fibrosis in rats by rebalancing Th1/Th2 cytokines

et al. 2021

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The present study aimed to investigate the effects of TGF-β1, tissue inhibitor of metalloproteinase (TIMP)-1 small interfering (si)RNA and TIMP-2 siRNA on hepatic fibrosis in rats and explore the T helper (Th)1/Th2 balance. Moreover, IFN-γ, IL-4 and IL-13 are the main cytokines associated with Th1/Th2 responses and have significant influence on the progression of hepatic fibrosis. The expression levels of IFN-γ, IL-4 and IL-13 in rats with hepatic fibrosis that were treated with siRNAs against the aforementioned molecules were measured using various techniques including immunohistochemical staining, western blotting and reverse transcription-quantitative PCR. The principal outcomes revealed the downregulation of IFN-γ and the upregulation of IL-4 and IL-13 in the model group compared with the normal group. Moreover, the expression of IFN-γ was significantly increased, while IL-4 and IL-13 demonstrated no significant difference in the TGF-β1 siRNA treatment group compared with the model group. The TIMP-1 and TIMP-2 siRNA treatment groups exhibited significantly increased expression levels of IFN-γ, but lower expression levels of IL-4 and IL-13 compared with the model group. These results indicated that TIMP-1 and TIMP-2 were improved antifibrotic targets compared with TGF-β1.

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Th1 and Th2 cytokines differentially regulate the transformation of Kupffer cells into multinucleated giant cells but similarly enhance the Kupffer cell-induced hepatic stellate cell proliferation

Cited by 3 publications

References 27 publications

The Detection of IRF-1 Promoter Polymorphisms and Their Possible Contribution to T Helper 1 Response in Chronic Hepatitis C

The Detection of IRF-1 Promoter Polymorphisms and Their Possible Contribution to T Helper 1 Response in Chronic Hepatitis C

Relationship between serum cytokine levels and histopathological changes of liver in patients with hepatitis B

Application of TGF‑β1, TIMP‑1 and TIMP‑2 small interfering RNAs can alleviate CCl₄‑induced hepatic fibrosis in rats by rebalancing Th1/Th2 cytokines

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Th1 and Th2 cytokines differentially regulate the transformation of Kupffer cells into multinucleated giant cells but similarly enhance the Kupffer cell-induced hepatic stellate cell proliferation

Cited by 3 publications

References 27 publications

The Detection of IRF-1 Promoter Polymorphisms and Their Possible Contribution to T Helper 1 Response in Chronic Hepatitis C

The Detection of IRF-1 Promoter Polymorphisms and Their Possible Contribution to T Helper 1 Response in Chronic Hepatitis C

Relationship between serum cytokine levels and histopathological changes of liver in patients with hepatitis B

Application of TGF‑β1, TIMP‑1 and TIMP‑2 small interfering RNAs can alleviate CCl4‑induced hepatic fibrosis in rats by rebalancing Th1/Th2 cytokines

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Application of TGF‑β1, TIMP‑1 and TIMP‑2 small interfering RNAs can alleviate CCl₄‑induced hepatic fibrosis in rats by rebalancing Th1/Th2 cytokines