Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.1 (RNase)
 16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alopecia areata is an autoimmune disease targeted at hair follicles with infiltrated T lymphocytes probably playing an important role in the pathogenesis. It was reported in 1985 that mechlorethamine was effective on alopecia areata patients. This has never been confirmed since. The aims of the study were to investigate the effects of mechlorethamine on balding C3H/HeJ mice affected with an alopecia-areata-like disease and to study the underlying mechanisms. Mice were treated on half of the dorsal skin with mechlorethamine and the contralateral side was treated with the vehicle ointment. After 10 wk of mechlorethamine therapy, a full pelage of hair covered the treated side in all the mice and was maintained during the study, whereas the vehicle-treated sides showed either no change or continued hair loss. Immunohistochemistry revealed that infiltrated CD4+ and CD8+ lymphocytes were eliminated from the treated side. In vitro cell viability assay showed that lymphocytes were much more sensitive to the cytotoxic effects of mechlorethamine than skin and hair follicular cells. RNase protection assay and real-time reverse transcription polymerase chain reaction showed that tumor necrosis factor alpha/beta, interleukin-12, and interferon-gamma were inhibited by mechlorethamine upon successful treatment. Our findings support that mechlorethamine restores follicular activity by selectively targeting infiltrated lymphocytes in vivo in alopecia-areata-affected mice.
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PMID:Topical mechlorethamine restores autoimmune-arrested follicular activity in mice with an alopecia areata-like disease by targeting infiltrated lymphocytes. 1260 52

Although many therapeutic modalities have been tested on alopecia areata, patient outcomes have been disappointing. Use of animal models would help to develop more efficient therapies as well as understanding therapeutic mechanisms. We have demonstrated that 0.1% topical anthralin ointment is 100% effective in restoring follicular activity in Dundee experimental balding rats. This is the most promising topical treatment for Dundee experimental balding rats among the therapeutic agents tested on this model. Various cytokines have been shown to be associated with the pathogenesis of alopecia areata. To test whether any of these cytokines might be modulated by anthralin, an RNase protection assay and the real-time polymerase chain reaction were performed to compare their expression between anthralin-treated and control skins. These experiments showed that expression of tumor necrosis factor-alpha and interferon-gamma was inhibited by anthralin, whereas expression of interleukin-1alpha/beta and their receptor antagonist, interleukin-1Ra, and interleukin-10 was stimulated by anthralin. In addition, using an antibody-based multi-immunoblotting technique, we found that certain signaling regulatory proteins were modulated by anthralin. Their potential roles in reversing the autoimmune-arrested follicular activity in Dundee experimental balding rats are discussed.
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PMID:Cytokines and signal transduction pathways mediated by anthralin in alopecia areata-affected Dundee experimental balding rats. 1289 1

Anthralin is a widely used topical anti-psoriatic drug that may have an immunomodulating effect on alopecia areata (AA) as it does in psoriasis. The aims of the present study were to investigate the effects of anthralin on hair growth in balding C3H/HeJ mice affected by an AA-like disease and to study the underlying mechanisms. Affected C3H/HeJ mice were treated daily for 10 weeks on half of the dorsal skin with 0.2% anthralin and the contra-lateral side was treated with the vehicle ointment. The percentage of surface hair coverage and hair density was graded weekly for both sides and hair growth indices were calculated using these two variables. Hair regrowth was observed in 9/14 mice on the treated sides. Four mice displayed near complete replacement of normal density and length hairs. All the vehicle-treated sides showed either no change or continued hair loss. An RNase protection assay (RPA) showed that expression of tumor necrosis factor-alpha (TNF-alpha) and -beta were inhibited by anthralin upon successful treatment. It appears that anthralin may be an effective therapy for C3H/HeJ mice with AA and certain cytokines may be involved in the therapeutic effects of anthralin on restoring hair regrowth in AA-affected C3H/HeJ mice.
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PMID:Restoration of hair growth in mice with an alopecia areata-like disease using topical anthralin. 1500 10