IFN-γ or IFN-α ameliorates chronic proliferative dermatitis by inducing expression of linear ubiquitin chain assembly complex.
نویسندگان
چکیده
The linear ubiquitin chain assembly complex (LUBAC) ubiquitin ligase complex, composed of HOIL-1L-interacting protein (HOIP), heme-oxidized IRP2 ubiquitin ligase-1L (HOIL-1L), and SHANK-associated RH domain protein, specifically generates linear polyubiquitin chains and is involved in NF-κB activation. Lack of SHANK-associated RH domain protein, which drastically reduces the amount of HOIP and HOIL-1L, causes chronic proliferative dermatitis (cpdm) in mice. Impaired NF-κB activation and augmented apoptosis have been implicated in the pathogenesis of cpdm in mice. In this study, we found that IFN-γ increased the amount of LUBAC by inducing HOIP and HOIL-1L mRNA transcription and enhanced the signal-induced NF-κB activation in embryonic fibroblasts, keratinocytes, and bone marrow-derived macrophages from wild-type and/or cpdm mice; however, IFN-γ failed to augment NF-κB activation in mouse embryonic fibroblasts lacking linear polyubiquitination activity of LUBAC. Moreover, s.c. injection of IFN-γ for 3 wk into the skin of cpdm mice increased the amount of HOIP, suppressed apoptosis, and ameliorated the dermatitis. Inhibition of keratinocyte apoptosis by IFN-γ injection suppressed neutrophil, macrophage, and mast cell infiltration and the amount of TNF-α in the skin of cpdm mice. Similarly, IFN-α also enhanced the amount of HOIP as well as NF-κB activation, inhibited apoptosis, and ameliorated cpdm dermatitis. These results indicate that the IFNs enhance NF-κB activation and ameliorate cpdm dermatitis by augmenting expression of HOIP and HOIL-1L and linear polyubiquitination activity of LUBAC.
منابع مشابه
IFN-g or IFN-a Ameliorates Chronic Proliferative Dermatitis by Inducing Expression of Linear Ubiquitin Chain Assembly Complex
متن کامل
بررسی غلظت اینترفرون- گاما، فاکتور نکروز تومور- آلفا، اینترلوکین- 13 و اینترلوکین- 4 در شیر مادر و ارتباط آن‌ها با درماتیت آتوپیک
Background: Atopic dermatitis (AD) is one of the most common chronic, highly pruritic and inflammatory skin diseases. The exclusive influence of breastfeeding in the prevention of inflammatory diseases is a matter of debate. In this study, we aimed to determine the concentration of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin-13 (IL-13) and interleukin-4 (IL-4) cyt...
متن کاملInterferon Gamma Unresponsiveness Due to Down-Regulation of IFN-γR Expression in Experimental Cutaneous Leishmaniasis
It is now well documented that interferon gamma (IFN-γ) is the indispensable cytokine for inducing protective immunity against experimental and human cutaneous leishmaniaisis. The importance of IFN-γ receptor (IFN-γR) has also been studied. In the present study, we made attempts to find out whether L. major infection is able to alter the expression of IFN-γR in vivo. In addition, we studied the...
متن کاملCloning and high level expression of bovine interferon gamma gene in eukaryotic cells (COS-7)
Interferon gamma (IFN-γ) is one of the key cytokines in defining T helper 1 lymphocyte immuneresponses. In this study, the bovine IFN-γ gene was cloned from spleen tissue RNA using the reversetranscription-polymerase chain reaction (RT-PCR). IFN-γ cDNA was sub-cloned and expressed inmammalian expression plasmid (pcDNA3.1(+)) under the control of the human cytomegalovirus (CMV)promoter. The pred...
متن کاملInterferon-γ (IFN-γ) does not mimic the catabolic effects of tumor necrosis factor-α (TNF-α)
Cachexia is common in chronic inflammatory diseases and is attributed, in part, to elevation of circulating pro-inflammatory cytokines. TNF-α is the prototype in this category. IFN-γ is also thought to play a role, but the evidence supporting this model is primarily indirect. To determine the direct effects of IFN-γ stimulation on muscle cells, we selected key components of the pro-catabolic si...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Journal of immunology
دوره 192 8 شماره
صفحات -
تاریخ انتشار 2014