Interleukin-6 and its receptors: A highly regulated and dynamic system

Wolf, Janina; Rose-John, Stefan; Garbers, Christoph

doi:10.1016/j.cyto.2014.05.024

Cited by 501 publications

(384 citation statements)

References 137 publications

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“…IL-6 is known to have both pro-and anti-inflammatory effects. 17 In contrast with the decreases in circulating IL-6 and kidney mRNA levels in ultrasound-treated animals previously described, IL-6 production ex vivo in response to LPS concentrations of 0.1-10 mg/ml was greater in splenocytes from ultrasound-treated mice compared with cells from sham mice (Figure 8). These results demonstrate functionally that splenocytes behave differently when exposed to ultrasound, therefore supporting either a direct or indirect effect of + cells were similar in spleens from control and ultrasound-treated mice.…”

Section: Ultrasound Modulates Splenocytecontrasting

confidence: 46%

“…51,52 However, these roles may not apply in all cases because IL-6 can be pro-or anti-inflammatory. 17 Furthermore, the complexity of the kidney and spleen microenvironment after ultrasound and IRI differs markedly from culture conditions of splenocytes examined ex vivo. Although future studies will be needed to understand our findings, they clearly demonstrate a functional change in splenocytes in response to ultrasound and in conjunction with prior work, also showing increased production of IL-6 and TNFa by splenocytes previously cultured with nicotine, further support the involvement of the cholinergic pathway in the protective effect of ultrasound.…”

Section: Neural Control Of Inflammationmentioning

confidence: 99%

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Ultrasound Modulates the Splenic Neuroimmune Axis in Attenuating AKI

Gigliotti

Huang

Bajwa

et al. 2015

Journal of the American Society of Nephrology

122

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We showed previously that prior exposure to a modified ultrasound regimen prevents kidney ischemiareperfusion injury (IRI) likely via the splenic cholinergic anti-inflammatory pathway (CAP) and a7 nicotinic acetylcholine receptors (a7nAChR). However, it is unclear how ultrasound stimulates the splenic CAP. Further investigating the role of the spleen in ischemic injury, we found that prior splenectomy (-7d) or chemical sympathectomy of the spleen with 6-hydroxydopamine (6OHDA; -14d) exacerbated injury after subthreshold (24-minute ischemia) IRI. 6-OHDA-induced splenic denervation also prevented ultrasoundinduced protection of kidneys from moderate (26-minute ischemia) IRI. Ultrasound-induced protection required hematopoietic but not parenchymal a7nAChRs, as shown by experiments in bone marrow chimeras generated with wild-type and a7nAChR -/-mice. Ultrasound protection was associated with reduced expression of circulating and kidney-derived cytokines. However, splenocytes isolated from mice 24 hours after ultrasound treatment released more IL-6 ex vivo in response to LPS than splenocytes from sham mice. Adoptive transfer of splenocytes from ultrasound-treated (but not sham) mice to naïve mice was sufficient to protect kidneys of recipient mice from IRI. Ultrasound treatment 24 hours before cecal ligation puncture-induced sepsis was effective in reducing plasma creatinine in this model of AKI. Thus, splenocytes of ultrasound-treated mice are capable of modulating IRI in vivo, supporting our ongoing hypothesis that a modified ultrasound regimen has therapeutic potential for AKI and other inflammatory conditions.

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Section: Ultrasound Modulates Splenocytecontrasting

confidence: 46%

Section: Neural Control Of Inflammationmentioning

confidence: 99%

Ultrasound Modulates the Splenic Neuroimmune Axis in Attenuating AKI

Gigliotti

Huang

Bajwa

et al. 2015

Journal of the American Society of Nephrology

122

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“…As gp130 is ubiquitously expressed, IL-6R expression determines whether a cell is responsive to classic signaling or trans-signaling. Although most soluble receptors are antagonist and compete with their transmembrane receptor, sIL-6Rα is an agonist of IL-6Rα (Wolf et al 2014). Classical IL-6R signaling seems to control central homeostatic processes (regulation of the neuroendocrine system), activates anti-inflammatory pathways and promotes the regeneration of tissue, whereas IL-6 trans-signaling activates proinflammatory pathways and plays an important role in many diseases and cancer (Wolf et al 2014, Kumari et al 2016.…”

Section: Biology and Functions Of Il-6mentioning

confidence: 99%

“…Although most soluble receptors are antagonist and compete with their transmembrane receptor, sIL-6Rα is an agonist of IL-6Rα (Wolf et al 2014). Classical IL-6R signaling seems to control central homeostatic processes (regulation of the neuroendocrine system), activates anti-inflammatory pathways and promotes the regeneration of tissue, whereas IL-6 trans-signaling activates proinflammatory pathways and plays an important role in many diseases and cancer (Wolf et al 2014, Kumari et al 2016. sIL-6Rα is generated by alternative splicing of IL-6 mRNA or by 'shedding', a limited proteolysis of extracellular region of the membrane-bound IL-6R carried out by transmembrane zinc-dependent proteases ADAM17 and ADAM10 (Yoshida et al 1996, Jones et al 2001.…”

Section: Biology and Functions Of Il-6mentioning

confidence: 99%

Programmed cell senescence: role of IL-6 in the pituitary

Sapochnik

Fuertes

Arzt

2017

Journal of Molecular Endocrinology

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IL-6 is a pleiotropic cytokine with multiple pathophysiological functions. As a key factor of the senescence secretome, it can not only promote tumorigenesis and cell proliferation but also exert tumor suppressive functions, depending on the cellular context. IL-6, as do other cytokines, plays important roles in the function, growth and neuroendocrine responses of the anterior pituitary gland. The multiple actions of IL-6 on normal and adenomatous pituitary function, cell proliferation, angiogenesis and extracellular matrix remodeling indicate its importance in the regulation of the anterior pituitary. Pituitary tumors are mostly benign adenomas with low mitotic index and rarely became malignant. Premature senescence occurs in slow-growing benign tumors, like pituitary adenomas. The dual role of IL-6 in senescence and tumorigenesis is well represented in pituitary tumor development, as it has been demonstrated that effects of paracrine IL-6 may allow initial pituitary cell growth, whereas autocrine IL-6 in the same tumor triggers senescence and restrains aggressive growth and malignant transformation. IL-6 is instrumental in promotion and maintenance of the senescence program in pituitary adenomas.

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“…/2016/ ТОМ 15/ № 5 ных с высоким риском преждевременных родов [27]. Чуть позднее, в 2014 г., немецкие ученые установи-ли связь преждевременных родов с полиморфизмом rs8192282 гена ребенка, кодирующего рецептор интер-лейкина 6, отвечающего за иммунную сигнализацию [28].…”

Section: вопросы современной педиатрииunclassified