• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.36 no.6
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• pp.481-489
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• 2010

Introduction: TLR-5, a member of the toll-like receptor (TLR) family, is a element of the type I transmembrane receptors, which are characterized by an intracellular signaling domain homolog to the interleukin-1 receptor. These receptors recognize microbial components, particularly bacterial flagellin. All-trans retinoic acid (atRA, tretinoin), a natural metabolite of vitamin A, acts as a growth and differentiation factor in many tissues, and is also needed for immune functions. In this study, THP-1 human macrophage-monocytes were used to examine the mechanisms by which atRA regulated the expression of TLR-5. Because the molecular mechanism underlying this regulation at the transcriptional level is also unclear, this study examined which putative transcription factors are responsible for TLR-5 expression by atRA in immune cells. Materials and Methods: This study examined whether atRA induces the expression of TLR-5 in THP-1 cells using reverse transcription-polymerase chain reaction (RT-PCR), and which transcription factors are involved in regulating the TLR-5 promoter in RAW264.7 cells using a reporter assay system. Western blot analysis was used to determine which signal pathway is involved in the expression of TLR-5 in atRA-treated THP-1 cells. Results: atRA at a concentration of 10 nM greatly induced the expression of TLR-5 in THP-1 cells. Human TLR-5 promoter contains three Sp-1/GC binding sites around -50 bp and two NF-kB binding sites at -380 bp and -160 bp from the transcriptional start site of the TLR-5 gene. Sp-1/GC is primarily responsible for the constitutive TLR-5 expression, and may also contribute to NF-kB at -160 bp to induce TLR-5 after atRA stimulation in THP-1 cells. The role of NF-kB in TLR-5 expression was further confirmed by inhibitor pyrrolidine dithiocarbamate (PDTC) experiments, which greatly reduced the TLR-5 transcription by 70-80%. Conclusion: atRA induces the expression of the human TLR-5 gene and NF-kB is a critical transcription factor for the atRA-induced expression of TLR-5. Accordingly, it is conceivable that retinoids are required for adequate innate and adaptive immune responses to agents of infectious diseases. atRA and various synthetic retinoids have been used therapeutically in human diseases, such as leukemia and other cancers due to the antiproliferative and apoptosis inducing effects of retinoids. Therefore, understanding the molecular regulatory mechanism of TLR-5 may assist in the design of alternative strategies for the treatment of infectious diseases, leukemia and cancers.

• Clinical and Experimental Pediatrics
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• v.54 no.3
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• pp.95-105
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• 2011

Since the successful introduction of all-trans-retinoic acid (ATRA) and its combination with anthracycline-containing chemotherapy, the prognosis for acute promyelocytic leukemia (APL) has markedly improved. With ATRA and anthracycline-based-chemotherapy, the complete remission rate is greater than 90%, and the long-term survival rate is 70-89%. Moreover, arsenic trioxide (ATO), which was introduced for APL treatment in 1994, resulted in excellent remission rates in relapsed patients with APL, and more recently, several clinical studies have been designed to explore its role in initial therapy either alone or in combination with ATRA. APL is a rare disease in children and is frequently associated with hyperleukocytosis, which is a marker for higher risk of relapse and an increased incidence of microgranular morphology. The frequency of occurrence of the promyelocytic leu-kemia/retinoic acid receptor-alpha (PML/$RAR{\alpha}$) isoforms bcr 2 and bcr 3 is higher in children than in adults. Although recent clinical studies have reported comparable long-term survival rates in patients with APL, therapy for APL in children is challenging because of the risk of early death and the potential long-term cardiac toxicity resulting from the need to use high doses of anthracyclines. Additional prospective, randomized, large clinical trials are needed to address several issues in pediatric APL and to possibly minimize or eliminate the need for chemotherapy by combining ATRA and ATO. In this review article, we discuss the molecular pathogenesis, diagnostic progress, and most recent therapeutic advances in the treatment of children with APL.

• Korean Journal of Psychosomatic Medicine
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• v.8 no.1
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• pp.31-45
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• 2000

Objectives : The present study was performed to reveal differences between female and male cases of alopecia in their alopecia related variables such as patterns of hair loss, psychiatric characteristics, associate illnesses, and methods of treatment, and to use them as basic materials for proper management and early prevention of the alopecia prone cases. Methods : In order to analysis the gender difference in hair losses, the subjects were divided into two subgroups as the 51 cases of female alopecia and the 42 cases of male alopecia, who had visited to the department of psychiatry consulted from the department of dermatology, Yongsan hopital, ChungAng University, Seoul, Korea, from January 1998 to December 1998. In data analysis, the subjects were statistically assesed by chi-squre test and analysis of varaiance, through SPSS-$PC^+$ 9.0V. Results : 1) Female subjects were more likely showed lower socio-economical level including lower eonomical level, lower educational level, or lower occupational level in their parent's job, were more likely to have larger number of siblings and to have many sisters comparison to the male cases. 2) Female subjects were more likely visited to the department of dermatology, more history of alopecia in their female family members, lesser history of alopecia in their male family members, more loss of hairs in vertex or frontal region of scalp, lesser loss of hairs in occipital region, and lesser nail changes in comparison to the male cases. 3) Female subjects were more suffered from intra-familial conflicts and economical changes, or their introverted personality makeup, lesser likely suffered from changes of business and health changes, and showed lesser conflicts related with poorer adaptaion in their job life. 4) Female subjects were more likely diagnosed as depression or conversion disorders, more frequently complaint anxiety symptoms or depressive symptoms, higher level of anxiety index, lesser complaint somatization or obsessive compulsive symptoms, and lesser diagnosed as anxiety disorder in comparison to the male cases. 5) Female subjects were more likely tended to show personality makeup such as the introverted, the lie, the repressed, or the feminine trends than the male cases. 6) Female subjects were more significantly treated by antianxiety drug such as etizolam and dermatological therapies include tretinoin, and lesser treated by clotiazepam and prednicarbonate in comparison to the male cases. Conclusion : From the facts that The most important factors in developing hair loss in the female subjects in comparison to the male cases seems to be closely correlated with the serious psychopathology such as the presence of mental disorders including depression, the presence of complaining anxiety or depressive symptomatology, the presence of stressful life events such as intrafamilial life changes, and the presence of personality makeup such as the introverted, the lie, the repressed, or the feminine trends, the authors confirmed that dermatologists act as the primary care physician are in a unique position to recognize psychiatric comorbidity and execute meaningful intervention for female patients with the alopecia with psychiatrists.