Interleukin-13 reduces hyperalgesia and the level of interleukin-1β in BALB/c mice infected with Leishmania major with an up-regulation of interleukin-6

Karam, Marc; Al-Kouba, Jane; Bazzi, Samer; Smith, Catherine; Leung, Lawrence C.

doi:10.1016/j.jneuroim.2011.02.003

Cited by 19 publications

(18 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, mRNA expression of anti-inflammatory cytokines, such as IL10, Ifn-α4, Socs3, and Tgf-β [27]–[30], decreased in the early post-surgical stages, confirming that cytokines were involved in the inflammation response within the osteoarthritic subchondral bone.…”

Section: Resultsmentioning

confidence: 76%

Gene Expression Analyses of Subchondral Bone in Early Experimental Osteoarthritis by Microarray

et al. 2012

View full text Add to dashboard Cite

Osteoarthritis (OA) is a degenerative joint disease that affects both cartilage and bone. A better understanding of the early molecular changes in subchondral bone may help elucidate the pathogenesis of OA. We used microarray technology to investigate the time course of molecular changes in the subchondral bone in the early stages of experimental osteoarthritis in a rat model. We identified 2,234 differentially expressed (DE) genes at 1 week, 1,944 at 2 weeks and 1,517 at 4 weeks post-surgery. Further analyses of the dysregulated genes indicated that the events underlying subchondral bone remodeling occurred sequentially and in a time-dependent manner at the gene expression level. Some of the identified dysregulated genes that were identified have suspected roles in bone development or remodeling; these genes include Alp, Igf1, Tgf β1, Postn, Mmp3, Tnfsf11, Acp5, Bmp5, Aspn and Ihh. The differences in the expression of these genes were confirmed by real-time PCR, and the results indicated that our microarray data accurately reflected gene expression patterns characteristic of early OA. To validate the results of our microarray analysis at the protein level, immunohistochemistry staining was used to investigate the expression of Mmp3 and Aspn protein in tissue sections. These analyses indicate that Mmp3 protein expression completely matched the results of both the microarray and real-time PCR analyses; however, Aspn protein expression was not observed to differ at any time. In summary, our study demonstrated a simple method of separation of subchondral bone sample from the knee joint of rat, which can effectively avoid bone RNA degradation. These findings also revealed the gene expression profiles of subchondral bone in the rat OA model at multiple time points post-surgery and identified important DE genes with known or suspected roles in bone development or remodeling. These genes may be novel diagnostic markers or therapeutic targets for OA.

show abstract

Section: Resultsmentioning

confidence: 76%

Gene Expression Analyses of Subchondral Bone in Early Experimental Osteoarthritis by Microarray

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Neuro-immune interactions may be crucial for the development of neuropathic pain (Ellis and Bennett, 2013), and similar pathomechanisms have been implied for depression (Furtado and Katzman, 2015). Interactions between pro- and anti-inflammatory systems seem to play a major role (Üçeyler et al, 2009), which is underlined by data on disturbed pain behavior in animal models of cytokine or immune component deficiency (Cunha et al, 1999; Vale et al, 2003; Schoeniger-Skinner et al, 2007; Karam et al, 2011; Üçeyler et al, 2011; Sun et al, 2016). …”

Section: Introductionmentioning

confidence: 99%

Differential Impact of miR-21 on Pain and Associated Affective and Cognitive Behavior after Spared Nerve Injury in B7-H1 ko Mouse

Karl

Grießhammer

Üçeyler

et al. 2017

Front. Mol. Neurosci.

View full text Add to dashboard Cite

MicroRNAs (miRNAs) are increasingly recognized as regulators of immune and neuronal gene expression and are potential master switches in neuropathic pain pathophysiology. miR-21 is a promising candidate that may link the immune and the pain system. To investigate the pathophysiological role of miR-21 in neuropathic pain, we assessed mice deficient of B7 homolog 1 (B7-H1), a major inhibitor of inflammatory responses. In previous studies, an upregulation of miR-21 had been shown in mouse lymphocytes. Young (8 weeks), middle-aged (6 months), and old (12 months) B7-H1 ko mice and wildtype littermates (WT) received a spared nerve injury (SNI). We assessed thermal withdrawal latencies and mechanical withdrawal thresholds. Further, we performed tests for anxiety-like and cognitive behavior. Quantitative real time PCR was used to determine miR-21 relative expression in peripheral nerves, and dorsal root ganglia (DRG) at distinct time points after SNI. We found mechanical hyposensitivity with increasing age of naïve B7-H1 ko mice. Young and middle-aged B7-H1 ko mice were more sensitive to mechanical stimuli compared to WT mice (young: p < 0.01, middle-aged: p < 0.05). Both genotypes developed mechanical and heat hypersensitivity (p < 0.05) after SNI, without intergroup differences. No relevant differences were found after SNI in three tests for anxiety like behavior in B7-H1 ko and WT mice. Also, SNI had no effect on cognition. B7-H1 ko and WT mice showed a higher miR-21 expression (p < 0.05) and invasion of macrophages and T cells in the injured nerve 7 days after SNI without intergroup differences. Our study reveals that increased miR-21 expression in peripheral nerves after SNI is associated with reduced mechanical and heat withdrawal thresholds. These results point to a role of miR-21 in the pathophysiology of neuropathic pain, while affective behavior and cognition seem to be spared. Contrary to expectations, B7-H1 ko mice did not show higher miR-21 expression than WT mice, thus, a B7-H1 knockout may be of limited relevance for the study of miR-21 related pain.

show abstract

“…In many animal models, pro-inflammatory cytokines are algesic and anti-inflammatory cytokines are analgesic, see [4] for review. The anti-inflammatory cytokines interleukin (IL)-4, IL-10, and IL-13 have analgesic effects in inflammatory and neuropathic pain models [5]–[10]. IL-4 and IL-13 share the same receptor and act via the signal transducer and activator of transcription 6 (STAT6) pathway.…”

Section: Introductionmentioning

confidence: 99%

IL-4 Deficiency Is Associated with Mechanical Hypersensitivity in Mice

et al. 2011

View full text Add to dashboard Cite

Interleukin-4 (IL-4) is an anti-inflammatory and analgesic cytokine that induces opioid receptor transcription. We investigated IL-4 knockout (ko) mice to characterize their pain behavior before and after chronic constriction injury (CCI) of the sciatic nerve as a model for neuropathic pain. We investigated opioid responsivity and measured cytokine and opioid receptor gene expression in the peripheral and central nervous system (PNS, CNS) of IL-4 ko mice in comparison with wildtype (wt) mice. Naïve IL-4 ko mice displayed tactile allodynia (wt: 0.45 g; ko: 0.18 g; p<0.001), while responses to heat and cold stimuli and to muscle pressure were not different. No compensatory changes in the gene expression of tumor necrosis factor-alpha (TNF), IL-1β, IL-10, and IL-13 were found in the PNS and CNS of naïve IL-4 ko mice. However, IL-1β gene expression was stronger in the sciatic nerve of IL-4 ko mice (p<0.001) 28 days after CCI and only IL-4 ko mice had elevated IL-10 gene expression (p = 0.014). Remarkably, CCI induced TNF (p<0.01), IL-1β (p<0.05), IL-10 (p<0.05), and IL-13 (p<0.001) gene expression exclusively in the ipsilateral spinal cord of IL-4 ko mice. The compensatory overexpression of the anti-inflammatory and analgesic cytokines IL-10 and IL-13 in the spinal cord of IL-4 ko mice may explain the lack of genotype differences for pain behavior after CCI. Additionally, CCI induced gene expression of μ, κ, and δ opioid receptors in the contralateral cortex and thalamus of IL-4 ko mice, paralleled by fast onset of morphine analgesia, but not in wt mice. We conclude that a lack of IL-4 leads to mechanical sensitivity; the compensatory hyperexpression of analgesic cytokines and opioid receptors after CCI, in turn, protects IL-4 ko mice from enhanced pain behavior after nerve lesion.

show abstract

Interleukin-13 reduces hyperalgesia and the level of interleukin-1β in BALB/c mice infected with Leishmania major with an up-regulation of interleukin-6

Cited by 19 publications

References 51 publications

Gene Expression Analyses of Subchondral Bone in Early Experimental Osteoarthritis by Microarray

Gene Expression Analyses of Subchondral Bone in Early Experimental Osteoarthritis by Microarray

Differential Impact of miR-21 on Pain and Associated Affective and Cognitive Behavior after Spared Nerve Injury in B7-H1 ko Mouse

IL-4 Deficiency Is Associated with Mechanical Hypersensitivity in Mice

Contact Info

Product

Resources

About