Human peritoneal mesothelial cells synthesize interleukin-6: Induction by IL-1β and TNFα

Abstract

Recent studies have demonstrated increased levels of IL-6 in the peritoneal cavity during CAPD peritonitis. The current investigation was initiated (i) to examine the human peritoneal mesothelial cell (HPMC) as a possible source of this secreted IL-6 and (ii) to characterize the released product and examine its regulation by other cytokines. Unstimulated HPMC under growth arrested conditions released IL-6 in a time dependent manner. After 24-hour HPMC IL-6 release (mean +/- SEM, N = 13) (expressed as pg/micrograms cell protein) was 1.67 +/- 0.33. Stimulation of HPMC with IL-1 beta or TNF alpha resulted in a time (increasing up to 48 hr) and dose dependent IL-6 generation. After 24 hours the levels induced by IL-1 beta and TNF alpha (both at 1000 pg/ml) were (mean +/- SEM, N = 13) 19.08 +/- 2.98 and 6.62 +/- 1.72, respectively. Stimulation with combinations of IL-1 beta and TNF alpha resulted in additive increases in IL-6 release. This release could be inhibited by co-incubation with anti-IL-1 beta and/or anti-TNF alpha antibodies. The level of released HPMC IL-6 measured by immunometric assay (ELISA) correlated directly with that detected in the 7TD1 IL-6 bioassay (r = 0.63; P < 0.001). Western blot analysis of concentrated HPMC supernatants using specific anti-IL-6 antibody demonstrated immunoreactive bands at 23 and 28 Kd following IL-1 beta or TNF alpha treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

IL-6 and soluble IL-6 receptors (sIL-6R and sgp130) in human pleural effusions: massive IL-6 production independently of underlying diseases

“…This is in keeping with the hypothesis that the pleura can spontaneously produce IL-6 whatever the conditions leading to pleural effusion. Numerous cells have been described to produce IL-6, including T and B lymphocytes, monocytes, fibroblasts, PMN, endothelial and mesothelial cells and a variety of tumour cells [2,4,22,23]. The normal pleura is mainly made up of fibroblasts and mesothelial cells, two candidates for IL-6 production by normal pleural cells.…”

“…IL-6 also acts as an accessory factor promoting T cell activation, B cell differentiation, transition of haematopoietic stem cells from the G 0 to the G 1 phase of the cell cycle and maturation of megacaryocytes. Many cell types, including monocytes/macrophages, fibroblasts, endothelial and mesothelial cells, keratinocytes, B and T cells, mast cells, chondrocytes, polymorphonuclear neutrophils (PMN), some nerve cells, and a variety of tumour cell lines, were shown to produce IL-6 [2][3][4][5].…”

Interleukin-10 gene transfer to peritoneal mesothelial cells suppresses peritoneal dissemination of gastric cancer cells due to a persistently high concentration in the peritoneal cavity

“…Therefore, we focused on the PMCs, since PMCs are abundant in the closed peritoneal cavity and have a potent capacity to produce various cytokines such as IL-1, IL-6, IL-8, G-CSF, VEGF and SDF-1. [20][21][22][23][24][25] We demonstrated that IL-10 levels were markedly high in the peritoneal lavage but low in plasma and not detectable in the nodules at 1 and 3 weeks after Ad-mIL-10 administration. Considering the transfection efficacy for PMCs in the in vitro study, these findings suggest that our aim in the present study of developing a system for continuous, focal production of IL-10 may have been established.…”

“…19 PMCs are abundant in the peritoneal cavity and have the potential to produce many cytokines, such as IL-1, IL-6, IL-8, granulocyte colony-stimulating factor (G-CSF), vascular endothelial growth factor (VEGF), and stromal cell-derived factor-1 (SDF-1). [20][21][22][23][24][25] Thus, PMCs may be involved in peritoneal metastasis. However, the precise role of these cells has not been fully investigated.…”

Interference of Peritoneal Dialysis Fluids with Cell Cycle Mechanisms

“…Peritoneal mesothelial cells play an essential role in maintaining peritoneal membrane homeostasis and thus structural and functional integrity. They secrete numerous cytokines and growth factors (30)(31)(32), contribute to peritoneal host defense (33) and prevent local frictions and adhesions by secretion of active surface substances and lubricants such as cancer antigen (CA) 125. CA125 has been used as a PD effluent surrogate marker of PMC mass (34).…”