CCL21/CCR7 Prevents Apoptosis via the ERK Pathway in Human Non-Small Cell Lung Cancer Cells

Previously, we confirmed that C-C chemokine receptor 7 (CCR7) promotes cell proliferation via the extracellular signal-regulated kinase (ERK) pathway, but its role in apoptosis of non-small cell lung cancer (NSCLC) cell lines remains unknown. A549 and H460 cells of NSCLC were used to examine the effect of CCL21/CCR7 on apoptosis using flow cytometry. The results showed that activation of CCR7 by its specific ligand, exogenous chemokine ligand 21 (CCL21), was associated with a significant decline in the percent of apoptosis. Western blot and real-time PCR assays indicated that activation of CCR7 significantly caused upregulation of anti-apoptotic bcl-2 and downregulation of pro-apoptotic bax and caspase-3, but not p53, at both protein and mRNA levels. CCR7 small interfering RNA significantly attenuated these effects of exogenous CCL21. Besides, PD98059, a selective inhibitor of MEK that disrupts the activation of downstream ERK, significantly abolished these effects of CCL21/CCR7. Coimmunoprecipitation further confirmed that there was an interaction between p-ERK and bcl-2, bax, or caspase-3, particularly in the presence of CCL21. These results strongly suggest that CCL21/CCR7 prevents apoptosis by upregulating the expression of bcl-2 and by downregulating the expression of bax and caspase-3 potentially via the ERK pathway in A549 and H460 cells of NSCLC

The allergic sensitization in infants with atopic eczema from different countries

No study has compared allergic sensitization patterns in infants with atopic eczema from different countries. The aim of this study was to investigate the patterns of allergic sensitization in a cohort of infants with atopic eczema participating in a multicentre, international study

Confirmation of the association between high levels of immunoglobulin E food sensitization and eczema in infancy: an international study

Background Studies of Australian infants have reported that more than 80% of those with moderate atopic eczema (AE) have high levels of IgE food sensitization (IgE-FS) that are commonly associated with IgE food allergy. Objectives To explore the relationship between high levels of IgE-FS and AE in a large cohort of young children with eczema participating in a multi-centre, international study. Methods Two thousand one hundred and eighty-four subjects (mean age 17.6 months, range 11.8-25.4; 1246 males) with active eczema from atopic families from 94 centres in 12 countries were studied. Clinical history, Scoring Atopic Dermatitis index as a measure of eczema severity and CAP-FEIA measurements for total IgE and IgE antibody levels to cow milk, egg and peanut were entered into a database. If CAP-FEIA levels exceeded previously reported age-specific cut-off levels for 95% positive predictive values (PPVs) for food allergy, subjects were defined as having high-risk IgE-FS (HR-IgE-FS). Results Serum was available from 2048 patients; 55.5% were atopic. The frequency of HR-IgE-FS to milk, egg and/or peanut was the greatest in patients whose eczema developed in the first 3 months of life and the least in those whose eczema developed after 12 months (P < 0.0001). In a regression analysis to allow for potential confounding factors, children with HR-IgE-FS had the most severe eczema and the youngest age of onset (P < 0.001); 64% of infants with severe eczema of onset-age <3 months had HR-IgE-FS. Conclusion Early-onset severe eczema in infancy was associated with HR-IgE-FS. Clinical implications Food allergies should be routinely assessed in infants with moderate or severe eczema. Capsule summary In eczematous infants, the earlier the age of onset, and the greater the severity of eczema, the greater the frequency of associated high levels of IgE-FS