Regulation of psoriasis, colitis, and the intestinal microbiota by clusterin.

Psoriasis, a chronic and systemic inflammatory disorder characterized by activation of the interleukin (IL)-23/IL-17 axis, may be associated with the intestinal microbiota through the so-called "gut-skin axis." Clusterin is a glycoprotein ubiquitously distributed in mammalian tissues; however, its role in psoriasis is unclear. Therefore, we evaluated the role of clusterin in psoriatic skin inflammation, systemic inflammation, and colitis using a murine model of IMQ-induced psoriasis. In IMQ-treated clusterin-knockout (clusterin-/-) mice, the expressions of inflammatory cytokines in clusterin-silenced human keratinocytes and intestinal microbial composition were analyzed. We also examined clusterin expression in the skin tissues of patients with psoriasis. IMQ-induced psoriatic skin inflammation is suppressed in clusterin-/- mice. Long-term administration of IMQ induced systemic inflammation and colitis; however, both were alleviated by the genetic deletion of clusterin. Genetic silencing of clusterin in human keratinocytes inhibited the production of inflammatory cytokines involved in the initiation and progression of psoriasis. The composition of the intestinal microbiota in IMQ-treated clusterin-/- and wild-type mice was different. Genetic deletion of clusterin suppressed the increase in the Firmicutes/Bacteroidetes (F/B) ratio. Skin tissues of patients with psoriasis showed high clusterin expression. In conclusion, inhibition of clusterin decreased psoriatic skin inflammation, systemic inflammation, colitis, and altered the F/B ratio in an IMQ-induced murine psoriasis model.

Toll-like receptor 4 regulates intestinal fibrosis via cytokine expression and epithelial-mesenchymal transition.

Intestinal fibrosis induced by chronic and recurrent colitis, which is exacerbated by bowel stenosis, stricture, and obstruction, is challenging to treat. Toll-like receptor 4 (TLR4) stimulates innate and acquired immunity in response to specific microbial components, but the role of TLR4 in intestinal fibrosis is largely unknown. We investigated its role in intestinal fibrosis using not only a murine fibrosis model but also human myofibroblasts and intestinal epithelial cells. Colon fibrosis was induced in TLR4-deficient (TLR4-/-) mice and its wild-type counterparts with 3% dextran sulfate sodium. Absence of TLR4 gene attenuated chronic inflammation and colonic macrophages infiltration; intestinal fibrosis and collagen deposition were suppressed. Also, the production of tumor necrosis factor-α, interleukin-12p40, and transforming growth factor-ß was reduced in TLR4-deficient peritoneal macrophages. TLR4 was silenced in CCD-18Co cells by small interfering RNA (siRNA), and matrix metalloproteinase-1, tissue inhibitor of metalloproteinase, and collagen α1 expression was evaluated. Role of TLR4 in epithelial-mesenchymal transition (EMT) was evaluated in HCT116 cells. Suppression of TLR4 transcription by siRNAs affected myofibroblasts activity, collagen synthesis, and EMT in the human cancer cell line. Thus, we suggest that TLR4 can be an essential mediator in intestinal chronic inflammation and fibrosis, indicating that TLR4 signaling is a potential therapeutic target for intestinal fibrosis.

Introduce and Promote the Home-based Hospice and Palliative Care / 한국호스피스완화의료학회지

PURPOSE: This study was conducted to understand public perception of home-based hospice and identify related factors. METHODS: Between August 19, 2014 and August 30, 2014, data were collected using an E-mail questionnaire that was filled by 1,500 adults who were over 20 years of age. Data were analyzed using descriptive statistics, chi2-test and logistic regression. RESULTS: Among the respondents, 15.9% were aware of home-based hospice care, and 61.3% were willing to receive home-based hospice care. The factors that influenced the participants' willingness to use home-based hospice services included residential district, religion and private health insurance. Respondents who lived in Seoul (OR: 1.56, 95% CI: 1.04~2.33), Gwangju/Jeolla province (OR: 2.02, 95% CI: 1.23~3.32), Busan/Ulsan/South Gyeongsang province (OR: 1.81, 95% CI: 1.17~2.82) were more well-aware of home-based hospice care than those who lived in Incheon/Gyeonggi province. The faithful were more informed about the services than those without non-faithful participants (Roman Catholics (OR: 2.03, 95% CI: 1.30~3.17), Protestants (OR: 1.76, 95% CI: 1.22~2.53). Participants who had a private health insurance plan knew more about the services than those without one (OR: 1.45, 95% CI: 1.03~2.04). CONCLUSION: First, it is necessary to improve perception of the public and healthcare providers regarding home-based hospice care. The government should review a measure to institutionalize operation of a palliative care team at hospitals and community home-based hospice care centers.