Interleukin-1 receptor type 1 is overexpressed in neurons but not in glial cells within the rat superficial spinal dorsal horn in complete Freund adjuvant-induced inflammatory pain

Holló, Krisztina; Ducza, László; Hegyi, Zoltán; Dócs, Klaudia; Hegedüs, Katalin; Bakk, Erzsébet; Papp, Ildikó; Kis, Gréta; Mészàr, Zoltán; Bardóczi, Zsuzsanna; Antal, Miklós

doi:10.1186/s12974-017-0902-x

Cited by 27 publications

(24 citation statements)

References 105 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported that IL-1β can induce astrocytic activation and astrogliosis (Herx and Yong, 2001). Our earlier findings (Holló et al, 2017) also suggest that during inflammatory pain IL-1β can act on spinal neurons and astrocytes. It has been revealed that IL-1β induce cell type-specific response in the cells of the CNS due to a neuron specific isoform of the IL-1 receptor accessory protein (IL-1RAcP), which is a required receptor partner in IL-1 signaling (Huang et al, 2011).…”

Section: Introductionsupporting

confidence: 68%

IL-1β Induced Cytokine Expression by Spinal Astrocytes Can Play a Role in the Maintenance of Chronic Inflammatory Pain

et al. 2020

Self Cite

View full text Add to dashboard Cite

It is now widely accepted that the glial cells of the central nervous system (CNS) are key players in many processes, especially when they are activated via neuron-glia or glia-glia interactions. In turn, many of the glia-derived pro-inflammatory cytokines contribute to central sensitization during inflammation or nerve injury-evoked pathological pain conditions. The prototype of pro-inflammatory cytokines is interleukin-1beta (IL-1β) which has widespread functions in inflammatory processes. Our earlier findings showed that in the spinal cord (besides neurons) astrocytes express the ligand binding interleukin-1 receptor type 1 (IL-1R1) subunit of the IL-1 receptor in the spinal dorsal horn in the chronic phase of inflammatory pain. Interestingly, spinal astrocytes are also the main source of the IL-1β itself which in turn acts on its neuronal and astrocytic IL-1R1 leading to cell-type specific responses. In the initial experiments we measured the IL-1β concentration in the spinal cord of C57BL/6 mice during the course of complete Freund adjuvant (CFA)-induced inflammatory pain and observed a peak of IL-1β level at the time of highest mechanical sensitivity. In order to further study astrocytic activation, primary astrocyte cultures from spinal cords of C57BL/6 wild type and IL-1R1 deficient mice were exposed to IL-1β in concentrations corresponding to the spinal levels in the CFA-induced pain model. By using cytokine array method we observed significant increase in the expressional level of three cytokines: interleukin-6 (IL-6), granulocyte-macrophage colony stimulating factor (GM-CSF) and chemokine (C-C motif) ligand 5 (CCL5 or RANTES). We also observed that the secretion of the three cytokines is mediated by the NFkB signaling pathway. Our data completes the picture of the IL-1β-triggered cytokine cascade in spinal astrocytes, which may lead to enhanced activation of the local cells (neurons and glia as well) and can lead to the prolonged maintenance of chronic pain. All these cytokines and the NFkB pathway can be possible targets of pain therapy.

show abstract

Section: Introductionsupporting

confidence: 68%

IL-1β Induced Cytokine Expression by Spinal Astrocytes Can Play a Role in the Maintenance of Chronic Inflammatory Pain

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Previous reports found IL-1R1 expression in the spinal cord dorsal horn and DRG neurons, and assigned the neuronal IL-1R1 as the mediator of IL-1β-induced thermal and mechanical allodynia 19 – 22 . Another report showed IL-1 signaling in muscle fibers contributes to idiopathic inflammatory myopathies 14 , 41 .…”

Section: Discussionmentioning

confidence: 91%

“…Previous studies have suggested that IL-1β induces mechanical and thermal allodynia through neuronal IL-1R1 in the spinal cord dorsal horn 19 and dorsal root ganglia (DRG) 20 – 22 . Unexpectedly, IL-1R1 mRNA was not found in neurons or tissue macrophages in these regions in our IL-1R1 GR/GR and CX3CR1GFP-IL-1R1 GR/GR mice; this result was confirmed by NeuN, neurofilament and GFP immunolabeling (Fig.…”

Section: Resultsmentioning

confidence: 99%

Salient type 1 interleukin 1 receptor expression in peripheral non-immune cells

Song

Zhu

Gorantla

et al. 2018

Sci Rep

View full text Add to dashboard Cite

Interleukin 1 is a pleiotropic cytokine that mediates diverse functions through its receptor, type I interleukin 1 receptor (IL-1R1). Most previous studies have focused on the expression and function of IL-1R1 in immune cells. Here we performed a comprehensive mapping of IL-1R1 distribution in multiple peripheral tissues using our IL-1R1 reporter (IL-1R1GR/GR) mice. This method yielded the highest sensitivity of in situ detection of IL-1R1 mRNA and protein. Besides validating previously reported IL-1R1 expression in the endocrine tissues including pituitary and pancreas, our results refuted previously reported exclusive IL-1R1 expression in neurons of the spinal cord dorsal horn and dorsal root ganglia (DRG). Instead, IL-1R1 expression was detected in endothelial cells within DRG, spinal cord, pancreas, colon, muscles and many immune organs. In addition, gp38+ fibroblastic reticular cells (FRCs), rather than tissue macrophages or other immune cells, were found to express high levels of IL-1R1 in colon and many immune organs. A functional test of spleen FRCs showed that they responded rapidly to systemic IL-1β stimulation in vivo. Taken together, this study provides a rigorous re-examination of IL-1R1 expression in peripheral tissues and reveals tissue FRCs as a previously unappreciated novel high IL-1R1-expressing cell type in peripheral IL-1 signaling.

show abstract

“…Although we and others (Wang et al, 2006;Holló et al, 2017) already showed that the spinal astrocytes express IL-1R1, we confirmed its expression on the cultured astrocytes (Figure 2A).…”

Section: Peripheral Inflammation Evoked By Cfa Injection Induced Elevsupporting

confidence: 65%

Image_1.tif

View full text Add to dashboard Cite

Interleukin-1 receptor type 1 is overexpressed in neurons but not in glial cells within the rat superficial spinal dorsal horn in complete Freund adjuvant-induced inflammatory pain

Cited by 27 publications

References 105 publications

IL-1β Induced Cytokine Expression by Spinal Astrocytes Can Play a Role in the Maintenance of Chronic Inflammatory Pain

IL-1β Induced Cytokine Expression by Spinal Astrocytes Can Play a Role in the Maintenance of Chronic Inflammatory Pain

Salient type 1 interleukin 1 receptor expression in peripheral non-immune cells

Image_1.tif

Contact Info

Product

Resources

About