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The involvement of the proteins of the IL-8 family (other type of chemokines) in the inflammation process is noted by their participation in the "respiratory distress" syndrome with allergic asthma, arthritis, psoriasis, and other chronic inflammatory reactions.
The source of IL-8 is mono-nuclear phagocytes, antigen-activated T-cells, cells of endothelium and epithelium, as well as neutrophils.
The main role of IL-8 in inflammation is neutrophil chemotaxis and stimulation of the activity of Granulocytes (category of white blood cells characterized by the presence of granules in their cytoplasm). Furthermore, IL-8, IL-1 and TNF-A influence the adhesive properties of neutrophils due to an increase in the expression of surface adhesive molecules, thus improving the inter-cellular interactions with the endothelial cells, which in turn contributes to an increase in the passing of the neutrophils through the walls of the vessels.
Thus, IL-8 contributes to strengthening of the reaction and to activation of the neutrophils with the inflammation. This Cytokine was discovered also in the synovial liquid of patients with rheumatic diseases, including those that accompany psoriasis.
The factor of the transcription - Nuclear factor kB (Nuclear factor-kappa B; NF-kB) causes the widest interest in the researchers because of the following special features: uncommon regulation, wide spectrum of controlled genes, central role in the immunological processes, complex structure of the subunits and the involvement in the development of inflammatory diseases.
Nuclear factor kB (Nuclear factor-kappa B; NF-kB) is activated in response to LPS, IL-1, TNF-A (TNFA; Tumor necrosis factor-alpha), virus infections, UV-light emission, B-activation or T-activation or in response to other physiological or non-physiological stimuli.
After phosphorylation by specific kinases - the so-called IkB kinases (IKK), the inhibiting protein of I-kB undergoes degradation by proteases of cytoplasm. The dissociation of I-kB from the inactive complex contributes to the activation of the remained NF-kB-subunits, which are translocated into the nucleus and connect with the specific NF-kB-sites in the promoter region of the NF-kB-inducible genes with the subsequent activation of the transcription of the genes, which code the proteins, that are implicated in the immune reactions, in the inflammation and that control the cellular growth
The inducible activation of nuclear factor kB stimulates the transcription of the inducible NO synthase (iNOS), which catalyzes the synthesis of NO; furthermore, in the number of such genes are Cytokines IL-2, IL-6, IL-8, G-CSf and other proteins. "Classical" dimer of nuclear factor kB is represented by NF-kB1 (p50) and RelA (p65) subunits.
This is the most intensively studied factor, although there are described many other combinations of homo- and heterodimers of NF-kB.
For example, there are heterodimers between RelB and p50 or RelB and p52. Different dimers possess different properties and are connected with the different sections of DNA, which makes it possible to differentially control the transcription of different genes. Between them there are also differences in the specificity to the cellular types, sub-cellular localization, and differentiated interaction with the forms of IkB etc.
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