Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aims of the present study were to investigate the expression of Toll-like receptor (TLR)2 on the peripheral blood monocytes of patients with nontuberculous mycobacterial (NTM) lung disease and healthy controls, and to assess the responses of these monocytes to TLR2 agonists such as Mycobacterium avium and lipoteichoic acid (LTA). Reverse transcriptase-PCR was used to analyse TLR2 mRNA expression in peripheral blood monocytes from 17 NTM patients and 10 healthy controls. mRNA and protein secretion levels were also determined for the cytokines interleukin (IL)-12 p40 and tumour necrosis factor (TNF)-alpha. Expression of TLR2 mRNA by peripheral blood monocytes after stimulation with M. avium or LTA was lower in NTM patients than in healthy controls. IL-12 p40 and TNF-alpha mRNA and cytokine secretion levels were also lower in patients than in healthy controls. Treatment with anti-TLR antibody decreased M. avium- and LTA-induced IL-12 p40 and TNF-alpha production in healthy controls, but not in NTM patients. The present results suggest that the downregulation of Toll-like receptor 2 and the resulting decreased production of interleukin-12 p40 and tumour necrosis factor-alpha following Mycobacterium avium or lipoteichoic acid stimulation may contribute to host susceptibility to nontuberculous mycobacterial lung disease.
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PMID:Impaired expression of Toll-like receptor 2 in nontuberculous mycobacterial lung disease. 1756 74

SKIN(2) ZK1300 is a three-dimensional human skin model consisting of multilayered dermal fibroblasts and well-differentiated epidermal keratinocyte layers, including a stratum corneum. To characterize this model better, constitutive levels of cytokine gene expression were determined. Reverse transcriptase-polymerase chain reaction (RT-PCR), followed by liquid hybridization to labelled internal probes, demonstrated that interleukin (IL)-1I, IL-1beta, IL-6, IL-8, IL-10, tumour necrosis factor (TNF)I, granulocyte macrophage-colony stimulating factor (GM-CSF), transforming growth factor (TGFbeta1) and IL-12 p35 mRNAs were constitutively expressed whereas IL-12 p40 was not. The contribution of the dermal component of this human skin model (Model ZK1100) was further characterized by determining constitutive cytokines expressed and their modulation by phorbol 12-myristate, 13-acetate (PMA). The dermal component, consisting of multilayered human dermal fibroblasts, constitutively expressed message for IL-1I, 1L-1beta, IL-6, IL-8, TGFbeta1, GM-CSF and IL-12 p35. Message was not detected for IL-10, TNFI or IL-12 p40. PMA treatment of the multilayered dermal fibroblasts increased steady-state mRNA levels of IL-1I, IL-1beta, IL-6, IL-8, GM-CSF and TGFbeta1, but did not induce IL-10, TNFI or IL-12 p40 expression at the dose and times tested. In summary, these studies demonstrate that the SKIN(2) three-dimensional human skin cultures, and their dermal component, constitutively express mRNA for an array of inflammatory and immunomodulatory cytokines, and that PMA exposure modulates mRNA levels of the dermal cytokines.
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PMID:Cytokine mRNA expression in an in vitro human skin model, SKIN(2). 2065 Feb 32

Interleukins are critical cytokines that are ubiquitously present in both vertebrates and invertebrates and constitute the front line of host innate immunity. Here, we identified and analyzed IL-12p40 from the Chinese sea bass Lateolabrax maculatus (LmIL-12p40). The LmIL-12p40 gene is expressed as a 1386-base pair transcript that encodes a polypeptide of 321 amino acids. Transcriptional expression analysis indicated that LmIL-12p40 mRNA was ubiquitously expressed in all tested tissues and had a comparatively high expression level in immune-associated tissues (head-kidney and intestines). Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) experiments showed that, after Vibro harveyi and Streptococus agalactiae infection, LmIL-12p40 mRNA expression was significantly up-regulated in the spleen, liver and head-kidney. To further clarify the immune function of LmIL-12p40 after bacterial challenge, the recombinant LmIL-12p40 protein was acquired using a prokaryotic expression method. Furthermore, the LmIL-12p40 dimer (LmIL-12p80) could be produced via protein-protein interactions by incubating p40 monomer expressed from the pET28a vector (pET28a-LmIL-12p40) with p40 monomer expressed from the pGEX4T-1 vector (pGEX4T-1-LmIL-12p40). The antimicrobial activity of the purified LmIL-12p40 and LmIL-12p80 proteins were further studied in vitro using a bacterial growth inhibition test (for both liquid and solid cultures) and in vivo (using a bacterial growth inhibition test with the head-kidney tissues). Furthermore, BL21 (DE3) E. coli cells transformed with the recombinant pET28a-LmIL-12p40 vector were dramatically protected in response to metal toxicity and H2O2-related oxidative stress. In summary, this study will provide foundational information regarding the role of LmIL-12p40 in defending against various biotic and abiotic stresses in fishes, which should help to further clarify the functional mechanism of interleukins.
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PMID:Molecular characterization and functional analysis of IL-12p40 from Chinese sea bass (Lateolabrax maculatus) under biotic and abiotic stresses. 3022 55


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