• Journal of Life Science
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• v.26 no.11
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• pp.1345-1354
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• 2016

Alopecia areata (AA) is a common and tissue-specific autoimmune disease of hair follicle resulting in the loss of hair on the scalp and elsewhere on the body. Hair follicles is a unique organ because it has its own immune system and hormonal milieu and has a different immune state at each hair cycle stage. The collapses of anagen-dependent hair follicle immune privilege arise autoimmune attack, inducing ectopic MHC class I expression in the hair follicle epithelium and autoantigen presentation to autoreactive CD8+T cells, which results in AA. Clinical and experimental studies have pointed that psychological stress may also influence the hair follicle immune/hormone systems and contribute to the induction of AA. The key pathogenesis of AA is associated with immune privilege guardians (including ACTH, ${\alpha}-MSH$, and $TGF-{\beta}$), natural killer group 2D-positive (NKG2D+) cells (including NK and CD8+T cells), and stress hormones (including CRH and substance P). Effective treatments for AA are still demanded. One of the future targets of treatment will be the modification of hair follicle immune privilege including stress. Recent studies have reported that JAK inhibitors and immunomodulators used in other autoimmune disease, such as psoriasis, atopic dermatitis, and rheumatoid arthritis, Tregs, platelet-rich plasma therapy, statins, and prostaglandin anaolgues are effective for AA. Here the article reviews the recent understanding in the pathogenesis associated with perifollicular endocrine/immunology and new treatments of AA.

• Korean Journal of Acupuncture
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• v.23 no.3
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• pp.133-160
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• 2006

Objectives : Scolopendrae Corpus has a broad array of clinical applications in Korean medicine, including treatment of inflammatory conditions such as arthritis. To explore the global gene expression profiles in human Raw cell lines treated with Scolopendrae Corpus herbal-acupuncture solution (SCHAS), cDNA microarray analysis was performed. Methods : The Raw 264.7 cells were treated with lipopolysaccharide (LPS), SCHAS, or both. The primary data was normalized by the total spots of intensity between two groups, and then normalized by the intensity ratio of reference genes such as housekeeping genes in both groups. The expression ratio was converted to log2 ratio. Normalized spot intensities were calculated into gene expression ratios between the control and treatment groups. Greater than 2 fold changes between two groups were considered to be of significance. Results : Of the 8 K genes profiled in this study, with a cut-off level of two-fold change in the expression, 20 genes (BCL2-related protein A1, MARCKS-like 1, etc.) were upregulated and 5 genes (activated RNA polymerase II transcription cofactor 4, calcium binding atopy-related autoantigen 1, etc.) downregulated following LPS treatment. 139 genes (kell blood group precursor (McLeod phenotype), ribosomal protein S7, etc.) were upregulated and 42 genes (anterior gradient 2 homolog (xenopus laevis), phosphodiesterase 8B, etc.) were downregulated following SCHAS treatment. And 10 genes (yeast saccharomyces cerevisiae intergeneic sequence 4-1, mitogen-activated protein kinase 1, etc.) were upregulated and 8 genes (spermatid perinuclear RNA binding protein, nuclear receptor binding protein 2, etc.) were downregulated following co-stimulation of SCHAS and LPS. Discussions : It is thought that microarrays will play an ever-growing role in the advance of our understanding of the pharmacological actions of SCHAS in the treatment of arthritis. But further studies are required to concretely prove the effectiveness of SCHAS.

• Molecules and Cells
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• v.37 no.5
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• pp.426-434
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• 2014

Peptidylarginine deiminase type 2 (PADI2) deiminates (or citrullinates) arginine residues in protein to citrulline residues in a $Ca^{2+}$-dependent manner, and is found in lymphocytes and macrophages. Vimentin is an intermediate filament protein and a well-known substrate of PADI2. Citrullinated vimentin is found in ionomycin-induced macrophage apoptosis. Citrullinated vimentin is the target of anti-Sa antibodies, which are specific to rheumatoid arthritis, and play a critical role in the pathogenesis of the disease. To investigate the role of PADI2 in apoptosis, we generated a Jurkat cell line that overexpressed the PADI2 transgene from a tetracycline-inducible promoter, and used a combination of 12-O-tetradecanoylphorbol-13-acetate and ionomycin to activate Jurkat cells. We found that PADI2 overexpression reduced the cell viability of activated Jurkat cells in1a dose- and time-dependent manner. The PADI2-overexpressed and -activated Jurkat cells presented typical manifestations of apoptosis, and exhibited greater levels of citrullinated proteins, including citrullinated vimentin. Vimentin overexpression rescued a portion of the cells from apoptosis. In conclusion, PADI2 overexpression induces apoptosis in activated Jurkat cells. Vimentin is involved in PADI2-induced apoptosis. Moreover, PADI2-overexpressed Jurkat cells secreted greater levels of vimentin after activation, and expressed more vimentin on their cell surfaces when undergoing apoptosis. Through artificially highlighting PADI2 and vimentin, we demonstrated that PADI2 and vimentin participate in the apoptotic mechanisms of activated T lymphocytes. The secretion and surface expression of vimentin are possible ways of autoantigen presentation to the immune system.