Trappin-2/Elafin Modulate Innate Immune Responses of Human Endometrial Epithelial Cells to PolyI∶C

BACKGROUND: Upon viral recognition, innate and adaptive antiviral immune responses are initiated by genital epithelial cells (ECs) to eradicate or contain viral infection. Such responses, however, are often accompanied by inflammation that contributes to acquisition and progression of sexually transmitted infections (STIs). Hence, interventions/factors enhancing antiviral protection while reducing inflammation may prove beneficial in controlling the spread of STIs. Serine antiprotease trappin-2 (Tr) and its cleaved form, elafin (E), are alarm antimicrobials secreted by multiple cells, including genital epithelia. METHODOLOGY AND PRINCIPAL FINDINGS: We investigated whether and how each Tr and E (Tr/E) contribute to antiviral defenses against a synthetic mimic of viral dsRNA, polyinosine-polycytidylic acid (polyI:C) and vesicular stomatitis virus. We show that delivery of a replication-deficient adenovector expressing Tr gene (Ad/Tr) to human endometrial epithelial cells, HEC-1A, resulted in secretion of functional Tr, whereas both Tr/E were detected in response to polyI:C. Moreover, Tr/E were found to significantly reduce viral replication by either acting directly on virus or through enhancing polyI:C-driven antiviral protection. The latter was associated with reduced levels of pro-inflammatory factors IL-8, IL-6, TNFα, lowered expression of RIG-I, MDA5 and attenuated NF-κB activation. Interestingly, enhanced polyI:C-driven antiviral protection of HEC-Ad/Tr cells was partially mediated through IRF3 activation, but not associated with higher induction of IFNβ, suggesting multiple antiviral mechanisms of Tr/E and the involvement of alternative factors or pathways. CONCLUSIONS AND SIGNIFICANCE: This is the first evidence of both Tr/E altering viral binding/entry, innate recognition and mounting of antiviral and inflammatory responses in genital ECs that could have significant implications for homeostasis of the female genital tract

Noncardiac chest pain: systematic review of the literature on prognosis

Edwin Meresh, John Piletz, Angelos Halaris Department of Psychiatry and Behavioral Neurosciences, Loyola University Medical Center, Stritch School of Medicine, Maywood, IL, USA Background: Noncardiac chest pain (NCCP) is defined as persistent angina-like chest pain with no evidence of cardiac disease. There is some controversy about the long-term morbidity and mortality outcomes of NCCP patients. Many studies have found no significant differences in death rates in chest pain patients without coronary artery disease compared to the general population. However, studies that include longer follow-up periods and a better characterization of the NCCP population reveal a twofold elevation in the relative risk of adverse cardiac events over 5–26 years. This review sought to identify studies in relation to cardiovascular and psychological prognosis of NCCP patients.Methods: PubMed database and reference lists from relevant publications were reviewed. Inclusion criteria were systematic reviews, prospective studies, and retrospective surveys from 1970 to 2011. Search terms were as follows: chest pain, noncardiac chest pain, nonspecific chest pain, unexplained chest pain, prognosis of noncardiac chest pain, prognosis of angina with normal angiography, and angina with normal coronary arteries.Results: Studies supporting worse outcome (cardiac morbidity and mortality; n=16) included 173,875 patients with mean age 57 and mean length of follow-up 7.5 years. Studies supporting good outcome (n=25) included 244,998 patients with age 50 and length of follow-up 5 years. Articles supporting poor psychological outcome (n=9) included 3,987 patients and length of follow-up 2 years.Conclusion: There are mixed data on long-term morbidity, cardiovascular adverse events, and mortality of NCCP patients. Some studies provide supporting evidence for poor outcome, while others provide evidence for positive outcome. However, many patients with NCCP have prolonged psychosocial comorbidity. The heterogeneity of NCCP and study populations limited definitive conclusions. However, many patients with NCCP have psychiatric morbidity and poor quality of life. Several questions remain about NCPP with respect to the psychopathology and pathophysiology of this condition. Whether NCCP patients have good or bad outcome requires careful risk stratification. Keywords: chest pain, noncardiac chest pain, anxiety, angina with normal coronary arteries, microvascular angina, prognosi