Airway epithelium is an important site for local vitamin D (VD) metabolism; this can be negatively affected by inflammatory mediators. VD is an important regulator of respiratory host defense, for... Show moreAirway epithelium is an important site for local vitamin D (VD) metabolism; this can be negatively affected by inflammatory mediators. VD is an important regulator of respiratory host defense, for example, by increasing the expression of hCAP18/LL-37. TGF-beta 1 is increased in chronic obstructive pulmonary disease (COPD), and known to decrease the expression of constitutive host defense mediators such as secretory leukocyte protease inhibitor (SLPI) and polymeric immunoglobulin receptor (pIgR). VD has been shown to affect TGF-beta 1-signaling by inhibiting TGF-beta 1-induced epithelial-to-mesenchymal transition. However, interactions between VD and TGF-beta 1, relevant for the understanding host defense in COPD, are incompletely understood. Therefore, the aim of the present study was to investigate the combined effects of VD and TGF-beta 1 on airway epithelial cell host defense mechanisms. Exposure to TGF-beta 1 reduced both baseline and VD-induced expression of hCAP18/LL-37, partly by increasing the expression of the VD-degrading enzyme CYP24A1. TGF-beta 1 alone decreased the number of secretory club and goblet cells and reduced the expression of constitutive host defense mediators SLPI, s/lPLUNC and pIgR, effects that were not modulated by VD. These results suggest that TGF-beta 1 may decrease the respiratory host defense both directly by reducing the expression of host defense mediators, and indirectly by affecting VD-mediated effects such as expression of hCAP18/LL-37. Show less
Roerink, M.E.; Schaaf, M.E. van der; Hawinkels, L.J.A.C.; Raijmakers, R.P.H.; Knoop, H.; Joosten, L.A.B.; Meer, J.W.M. van der 2018
Background: Serum TGF-beta 1 concentrations are reported to be elevated in chronic fatigue syndrome (CFS). However, measurement of circulating cytokines is a complex procedure and control of pre... Show moreBackground: Serum TGF-beta 1 concentrations are reported to be elevated in chronic fatigue syndrome (CFS). However, measurement of circulating cytokines is a complex procedure and control of pre-analytical procedures is essential. The objective of the current study was to measure circulating TGF-beta 1 concentrations in CFS patients compared to healthy controls, taking into account differences in pre-analytical procedures.Methods: Two cohorts of female CFS patients were included. In both studies patients were asked to bring a healthy, age-matched control. At baseline, TGF-beta 1 levels were measured in plasma and additionally P-selectin, a marker of platelet activity, was determined in a subgroup of participants.Results: 50 patients and 48 controls were included in cohort I, and 90 patients and 29 controls in cohort II. Within the cohorts there were no differences in TGF-beta 1 concentrations. However, between the cohorts there was a large discrepancy, which appeared to be caused by differences in g-force of the centrifuges used. The lower g-force used in cohort II (1361 g) caused more platelet activation, reflected by higher p-selectin concentrations, compared to cohort I (p < 0.0001), which was confirmed in a second independent experiment. There was a correlation between TGF-beta 1 and p-selectin concentrations (r 0.79, p < 0.0001).Conclusion: These results demonstrate that control of pre-analytical procedures is an essential aspect when measuring circulating cytokines. No evidence for enhanced TGF-beta 1 in patients with CFS was found. Show less
Janson, D.; Saintigny, G.; Zeypveld, J.; Mahe, C.; Ghalbzouri, A. el 2014
