Constitutive and inducible thymic stromal lymphopoietin expression in human airway smooth muscle cells: role in chronic obstructive pulmonary disease

Abstract

Thymic stromal lymphopoietin (TSLP) is a novel cytokine that triggers dendritic cell-mediated T helper (Th)-2 inflammatory responses. Previous studies have demonstrated that human airway smooth muscle cells (HASMC) play a critical role in initiating or perpetuating airway inflammation by producing chemokines and cytokines. In this study, we first evaluated the expression of TSLP in primary HASMC and investigated how proinflammatory cytokines (TNF-alpha and IL-1beta) and Th-2 cytokines (IL-4, IL-9) regulate TSLP production from HASMC. TSLP mRNA and protein were assessed by real-time RT-PCR, ELISA, and immunofluorescence from primary HASMC cultures. Primary HASMC express constitutive level of TSLP. Incubation of HASMC with IL-1 or TNF-alpha resulted in a significant increase of TSLP mRNA and protein release from HASMC. Furthermore, combination of IL-1beta and TNF-alpha has an additive effect on TSLP release by HASMC. Primary HASMC pretreated with inhibitors of p38 or p42/p44 ERK MAPK, but not phosphatidylinositol 3-kinase, showed a significant decrease in TSLP release on IL-1beta and TNF-alpha treatment. Furthermore, TSLP immunoreactivity was present in ASM bundle from chronic obstructive pulmonary disease (COPD) and to lesser degree in normal subjects. Taken together, our data provide the first evidence of IL-1beta- and TNF-alpha-induced TSLP expression in HASMC via (p38, p42/p44) MAPK signaling pathways. Our results raise the possibility that HASMC may play a role in COPD airway inflammation via TSLP-dependent pathway.

Helicobacter pylori genotypes among patients in a university hospital in Egypt: identifying the determinants of disease severity

“…Amplification cycles were performed with Cyclogene Thermal Cycler (Techne, England), as mentioned elsewhere. 5,[7][8][9] For each batch of PCR reactions a positive internal control amplifying the human housekeeping gene glyceraldehydes-3-phosphate dehydrogenase (GAPDH), 12 and a negative control were included. PCR products were analyzed in parallel with a DNA MW-marker (Fermentas) by electrophoresis on 2% agarose gel.…”

Multifaceted mechanisms in COPD: inflammation, immunity, and tissue repair and destruction

“…CXCL10/IP-10 is a potent chemoattractant for human monocytes, neutrophils, natural killer cells and T-cells, preferentially Th1 cells. Thymic stromal lymphopoietin is expressed in airway smooth muscle of patients with COPD [143] and may trigger DC-mediated Th2 inflammatory responses. Finally, airway smooth muscle cells are an important source of connective tissue growth factor (CTGF) and TGF-b [144,145].…”

Thymic Stromal Lymphopoietin Receptor-Mediated IL-6 and CC/CXC Chemokines Expression in Human Airway Smooth Muscle Cells: Role of MAPKs (ERK1/2, p38, and JNK) and STAT3 Pathways

“…Written informed consent for airway smooth muscle (ASM) harvesting was obtained from all patients. HASM cells were cultured and maintained as described earlier (22)(23)(24)(25)(26).…”