No abstract

Cystic fibrosis (CF), the most common life-threatening inherited disease in Caucasians, is due to mutations in the CF transmembrane conductance regulator (CFTR) gene and is characterized by airways chronic inflammation and pulmonary infections. The inflammatory response is not secondary to the pulmonary infections. Indeed, several studies have shown an increased proinflammatory activity in the CF tissues, regardless of bacterial infections, because inflammation is similarly observed in CFTR-defective cell lines kept in sterile conditions. Despite recent studies that have indicated that CF airway epithelial cells can spontaneously initiate the inflammatory cascade, we still do not have a clear insight of the molecular mechanisms involved in this increased inflammatory response. In this study, to understand these mechanisms, we investigated ex vivo cultures of nasal polyp mucosal explants of CF patients and controls, CFTR-defective IB3-1 bronchial epithelial cells, C38 isogenic CFTR corrected, and 16HBE normal bronchial epithelial cell lines. We have shown that a defective CFTR induces a remarkable up-regulation of tissue transglutaminase (TG2) in both tissues and cell lines. The increased TG2 activity leads to functional sequestration of the anti-inflammatory peroxisome proliferator-activated receptor γ and increase of the classic parameters of inflammation, such as TNF-α, tyrosine phosphorylation, and MAPKs. Specific inhibition of TG2 was able to reinstate normal levels of peroxisome proliferator-activated receptor-γ and dampen down inflammation both in CF tissues and CFTR-defective cells. Our results highlight an unpredicted central role of TG2 in the mechanistic pathway of CF inflammation, also opening a possible new wave of therapies for sufferers of chronic inflammatory diseases.

here are many questions and concerns about the coronavirus disease 2019 (COVID-19), including its implications for breastfeeding. 1 This commentary draws on a statement and recommendations recently issued by the Regional Office for Europe of the World Health Organization with the contribution of the European Pediatric Association-Union of National European Pediatric Societies and Associations and other main European pediatric organizations. 1 Our aim is to provide pediatricians with further guidance on breastfeeding and related safety measures during COVID-19, particularly in instances where a mother has or may have COVID-19. The COVID-2019 epidemic, caused by severe acute respiratory syndrome coronavirus 2, was first identified in Hubei Province China in December 2019, and has subsequently spread globally, placing extensive pressure on health systems and posing a major public health challenge worldwide. 2 On March 11, 2020, the World Health Organization (WHO) declared the outbreak a pandemic. 3 At the time, little was known about COVID-19 or its effects on the general population, and even less was known about how it could influence specific populations such as pregnant women, infants, or children. Reports show that children at all ages are sensitive to COVID-19, with no significant gender difference. 4 Clinical manifestations of children's COVID-19 cases are less severe than in adults' patients, and a review of 72 314 cases by the Chinese Center for Disease Control and Prevention showed that <1% of the cases were in children <10 years of age. 5 Additional information about COVID-19 infection among children is increasing over time, but questions remain, including questions about breastfeeding, particularly in instances when a mother may be infected with COVID-19. 6,7 The protection, promotion, and support of breastfeeding are a priority for public health and WHO has been continuously compiling evidence on the effect of COVID on mothers and children. 3,8,9

A r t i c l e A m e n d m e n t s4Concerns were recently raised with regard to the immunoblot images in Figure 5B, and it was unclear to the Editorial Board whether the position of the bands in lane 2 of the total IRS-1 blot and the O-GlcNAc was consistent with stripping and reprobing of the same membrane. An investigative committee at the University of Foggia found no evidence for image manipulation after comprehensive analysis of the available images by a noted expert in digital image analysis; however, the original raw data were unavailable for review due to a flood in the region. The authors have therefore performed a replicate experiment; the results (shown at right) are consistent with the findings originally reported in the paper.