Effects of chemokines on proliferation and apoptosis of human mesangial cells

Abstract

BackgroundProliferation and apoptosis of mesangial cells (MC) are important mechanisms during nephrogenesis, for the maintenance of glomerular homeostasis as well as in renal disease and glomerular regeneration. Expression of chemokines and chemokine receptors by intrinsic renal cells, e.g. SLC/CCL21 on podocytes and CCR7 on MC is suggested to play a pivotal role during these processes. Therefore the effect of selected chemokines on MC proliferation and apoptosis was studied.MethodsProliferation assays, cell death assays including cell cycle analysis, hoechst stain and measurement of caspase-3 activity were performed.ResultsA dose-dependent, mesangioproliferative effect of the chemokine SLC/CCL21, which is constitutively expressed on human podocytes was seen via activation of the chemokine receptor CCR7, which is constitutively expressed on MC. In addition, in cultured MC SLC/CCL21 had a protective effect on cell survival in Fas-mediated apoptosis. The CXCR3 ligands IP-10/CXCL10 and Mig/CXCL9 revealed a proproliferative effect but did not influence apoptosis of MC. Both the CCR1 ligand RANTES/CCL5 and the amino-terminally modified RANTES analogue Met-RANTES which blocks CCR1 signalling had no effect on proliferation and apoptosis.ConclusionsThe different effects of chemokines and their respective receptors on proliferation and apoptosis of MC suggest highly regulated, novel biological functions of chemokine/chemokine receptor pairs in processes involved in renal inflammation, regeneration and glomerular homeostasis.

The Multiple Personalities of the Chemokine Receptor CCR7 in Dendritic Cells

“…At least in T cells, it has been shown that CCR7 may control adhesion by regulating the activity of different integrins (32,48). CCR7 has also been described to regulate the proliferation in mesangial cells (42), T cells (45, 49), and hemopoietic precursor cells (21). Finally, recently, it has been shown that CCR7 regulates the invasive ability of carcinoma cells (50).…”

“…Concerning the regulation of the cytoarchitecture, it has been shown that stimulation of CCR7 induces filopodia formation in mesangial cells (38) and morphological polarization in T cells (39,40). Stimulation of CCR7 has also been shown to protect mesangial cells and CD8 T cells from CD95-and etoposide-induced apoptosis, respectively (41)(42)(43). Moreover, CCR7 regulates the migratory speed of naive T cells (40) and human squamous cell carcinoma (44).…”

Expression of a functional CCR7 chemokine receptor inhibits the post-intravasation steps of metastasis in malignant murine mammary cancer cells

“…CCR7 expression did not consistently alter any of the in vitro growth features examined, including proliferation in the presence of CCL21. A few non-leukocyte cell types expressing chemokine receptors were reported to have increased proliferation in the presence of the appropriate chemokine; CCR7-positive kidney mesangial cells showed a proliferative response to CCL21 (25,26), whereas CXCR4-positive human pancreatic tumor cells had enhanced proliferation in the presence of CXCL12 (27). Our data show that CCR7-expressing mammary cancer cells behave differently from other CCR7-expressing non-leukocyte cell types.…”

Peculiarities of the distribution and expression dynamics of apoptosis marker Bax in patients with rectal cancer under the influence of neoadjuvant chemoradiotherapy with the usage of nitric oxide precursor

“…Гіперекспресія макрофагами ко-лонієстимулюючого фактора у відповідь на променеве пошкодження сприяє їх поширенню у фокусі ураження, при цьому, синтезуючи цитокіни, вони виконують функ-цію клітинних ефекторів хронічного запалення. Висока концентрація цитокінів і профібротичних молекул, серед яких інтерлейкін-8, фактор некрозу пухлин-μ, ендотелін, TGF-β у ділянках інфільтрації зумовлює фіброзоутворен-ня, що є одним з індукторів апоптозу [6]. Так, колаген І і фібронектин, які є компонентами фіброзного матеріалу склеротично змінених ділянок РПК, площа котрих через місяць після НХПТ становить понад 40% площі зрізів пухлини, поряд з окисними модифікаціями компонентів ремодельованого фіброзного матриксу протягом трива-лого часу після завершення курсу НХПТ є потужними індукторами сигнальних шляхів апоптозу [6].…”