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Parathyroid hormone-related protein modulates inflammation in mouse mesangial cells and blunts apoptosis by enhancing COX-2 expression
- Source :
- American journal of physiology. Cell physiology. 314(2)
- Publication Year :
- 2017
-
Abstract
- Injury of mesangial cells (MC) is a prominent feature of glomerulonephritis. Activated MC secrete inflammatory mediators that induce cell apoptosis. Parathyroid hormone-related peptide (PTHrP) is a locally active cytokine that enhances cell survival and is upregulated by proinflammatory factors in many cell types. The aim of this study was to analyze the regulation of PTHrP expression by inflammatory cytokines and to evaluate whether PTHrP itself acts as a proinflammatory and/or survival factor on male murine MC in primary culture. Our results showed that IL-1β (10 ng/ml) and TNF-α (10 ng/ml) rapidly and transiently upregulated PTHrP expression in MC. The effects of IL-1β were both transcriptional and posttranscriptional, with stabilization of the PTHrP mRNA by human antigen R (HuR). Proteome profiler arrays showed that PTHrP itself enhanced cytokines within 2 h in cell lysates, mainly IL-17, IL-16, IL-1α, and IL-6. PTHrP also stimulated sustained expression (2–4 h) of chemokines, mainly regulated upon activation normal T cell expressed and secreted (RANTES)/C-C motif chemokine 5 (CCL5) and macrophage inflammatory protein-2 (MIP-2)/C-X-C motif chemokine 2 (CXCL2), thymus and activation-regulated chemokine (TARC)/CCL17, and interferon-inducible T cell α-chemoattractant (I-TAC)/CXCL11. Moreover, PTHrP markedly enhanced cyclooxygenase-2 (COX-2) expression and elicited its autoinduction through the activation of the NF-κB pathway. PTHrP induced MC survival via the COX-2 products, and PTHrP overexpression in MC blunted the apoptotic effects of IL-1β and TNF-α. Altogether, these findings suggest that PTHrP functions as a booster of glomerular inflammatory processes and may be a negative feedback loop preserving MC survival.
- Subjects :
- 0301 basic medicine
Male
medicine.medical_specialty
Time Factors
Physiology
Interleukin-1beta
Peptide
Inflammation
Apoptosis
Biology
03 medical and health sciences
Glomerulonephritis
Internal medicine
Parathyroid hormone-related peptide
medicine
Animals
Secretion
Cells, Cultured
chemistry.chemical_classification
Parathyroid hormone-related protein
Tumor Necrosis Factor-alpha
NF-kappa B
Parathyroid Hormone-Related Protein
Cell Biology
medicine.disease
Peptide Fragments
Up-Regulation
Mice, Inbred C57BL
030104 developmental biology
Endocrinology
chemistry
Cyclooxygenase 2
Mesangial Cells
Cancer research
medicine.symptom
Inflammation Mediators
hormones, hormone substitutes, and hormone antagonists
Signal Transduction
Subjects
Details
- ISSN :
- 15221563
- Volume :
- 314
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- American journal of physiology. Cell physiology
- Accession number :
- edsair.doi.dedup.....5d4e96028e2bdb1a9010f27bad096d88