Cytokines, such as interleukins, are crucial in regulating critical cell signaling pathways as well as being major contributors to inflammatory response and are upregulated during ligament and tendon injuries. The genes encoding key interleukins, such as IL1B and IL6 as well as interleukin receptor IL6R, were chosen as candidate genes for association with soft tissue injuries. The aim of the case-control study was to verify the hypothesis that sequence variants rs1143627, rs16944, rs1800795, rs2228145 in the IL1B, IL6 and IL6R genes are associated with ACL rupture susceptibility in a Polish population. Among four analyzed SNPs, the rs1800795 IL6 gene polymorphism was found to be the only one significantly associated with ACL rupture (p = 0.010, p = 0.022, p = 0.004 for codominant, recessive and overdominant models, respectively; odds ratio = 1.74, 95% CI 1.08-2.81, sex adjusted p = 0.032 for recessive model). With reference to the other analyzed polymorphisms, we failed to show significant differences in the genotype and allele frequencies for IL6R rs2228145as well as IL1B rs16944 and rs1143627 (analyzed alone or in haplotype combination) between the ACL rupture group and the healthy control group among Polish participants. Due to the nature of case-control studies, the results of this study need to be confirmed in independent studies with larger sample sizes.
- MeSH
- dospělí MeSH
- frekvence genu MeSH
- genetická predispozice k nemoci MeSH
- genotyp MeSH
- interleukin-1beta genetika MeSH
- interleukin-6 genetika MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé MeSH
- mladý dospělý MeSH
- poranění předního zkříženého vazu genetika MeSH
- receptory interleukinu-6 genetika MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Polsko MeSH
The occurrence and development of lung cancer is closely related to inflammation. Thus, we conducted the present study to investigate the effects of IL-37 (Interleukin 37), a newly identified anti-inflammatory factor, on non-small cell lung cancer (NSCLC), which accounts for about 85% of all lung cancers. To address the function of IL-37 in NSCLC, we first evaluated IL-37 expression in the human NSCLC tissues; then the IL-37 function was assessed in vitro and in vivo in a xenografted lung tumor model. IL-37 was barely expressed in the NSCLC tissue but highly expressed in the adjacent normal tissue. This expression profile was validated by ELISA (Enzyme-linked immunoassay), western blot and immunohistochemical staining. Recombinant IL-37 could suppress cell migration, invasion and proliferation and promote cell apoptosis in NSCLC cell line A549 and SK-MES-1. IL-37 inhibited the IL-6/STAT3 pathway and also the downstream targets Bcl-2, NEDD9 and Cyclin D1. Overexpressing IL-6 or constitutive active STAT3 eliminated the anti-tumor effects of IL-37. Furthermore, IL-37 expression in vivo could inhibit the cancer development. Our results showed that IL-37 plays an inhibitory role in lung cancer development, possibly through IL-6/STAT3 pathway.
- MeSH
- interleukin-1 genetika metabolismus MeSH
- lidé MeSH
- mediátory zánětu metabolismus MeSH
- nádorová transformace buněk imunologie MeSH
- nemalobuněčný karcinom plic * genetika metabolismus patologie MeSH
- receptory interleukinu-6 antagonisté a inhibitory genetika metabolismus MeSH
- signální transdukce MeSH
- transkripční faktor STAT3 antagonisté a inhibitory genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
BACKGROUND: IL-6 is a typical injury-induced mediator. Together with its receptors, IL-6 contributes to both induction and maintenance of neuropathic pain deriving from changes in activity of primary sensory neurons in dorsal root ganglia (DRG). We used in situ hybridization to provide evidence of IL-6 and IL-6 receptors (IL-6R and gp130) synthesis in DRG along the neuraxis after unilateral chronic constriction injury (CCI) of the sciatic nerve as an experimental model of neuropathic pain. RESULTS: All rats operated upon to create unilateral CCI displayed mechanical allodynia and thermal hyperalgesia in ipsilateral hind paws. Contralateral hind paws and forepaws of both sides exhibited only temporal and nonsignificant changes of sensitivity. Very low levels of IL-6 and IL-6R mRNAs were detected in naïve DRG. IL-6 mRNA was bilaterally increased not only in DRG neurons but also in satellite glial cells (SGC) activated by unilateral CCI. In addition to IL-6 mRNA, substantial increase of IL-6R mRNA expression occurred in DRG neurons and SGC following CCI, while the level of gp130 mRNA remained similar to that of DRG from naïve rats. CONCLUSIONS: Here we evidence for the first time increased synthesis of IL-6 and IL-6R in remote cervical DRG nonassociated with the nerve injury. Our results suggest that unilateral CCI of the sciatic nerve induced not only bilateral elevation of IL-6 and IL-6R mRNAs in L4-L5 DRG but also their propagation along the neuraxis to remote cervical DRG as a general neuroinflammatory reaction of the nervous system to local nerve injury without correlation with signs of neuropathic pain. Possible functional involvement of IL-6 signaling is discussed.
- MeSH
- hybridizace in situ MeSH
- interleukin-6 genetika MeSH
- krysa rodu rattus MeSH
- messenger RNA metabolismus MeSH
- modely nemocí na zvířatech MeSH
- nemoci sedacího nervu genetika MeSH
- neuralgie genetika MeSH
- neuroglie metabolismus MeSH
- potkani Wistar MeSH
- receptory interleukinu-6 genetika MeSH
- spinální ganglia metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Current research implicates interleukin (IL)-6 as a key component of the nervous-system response to injury with various effects. METHODS: We used unilateral chronic constriction injury (CCI) of rat sciatic nerve as a model for neuropathic pain. Immunofluorescence, ELISA, western blotting and in situ hybridization were used to investigate bilateral changes in IL-6 protein and mRNA in both lumbar (L4-L5) and cervical (C7-C8) dorsal root ganglia (DRG) following CCI. The operated (CCI) and sham-operated (sham) rats were assessed after 1, 3, 7, and 14 days. Withdrawal thresholds for mechanical hyperalgesia and latencies for thermal hyperalgesia were measured in both ipsilateral and contralateral hind and fore paws. RESULTS: The ipsilateral hind paws of all CCI rats displayed a decreased threshold of mechanical hyperalgesia and withdrawal latency of thermal hyperalgesia, while the contralateral hind and fore paws of both sides exhibited no significant changes in mechanical or thermal sensitivity. No significant behavioral changes were found in the hind and fore paws on either side of the sham rats, except for thermal hypersensitivity, which was present bilaterally at 3 days. Unilateral CCI of the sciatic nerve induced a bilateral increase in IL-6 immunostaining in the neuronal bodies and satellite glial cells (SGC) surrounding neurons of both lumbar and cervical DRG, compared with those of naive control rats. This bilateral increase in IL-6 protein levels was confirmed by ELISA and western blotting. More intense staining for IL-6 mRNA was detected in lumbar and cervical DRG from both sides of rats following CCI. The DRG removed from sham rats displayed a similar pattern of staining for IL-6 protein and mRNA as found in naive DRG, but there was a higher staining intensity in SGC. CONCLUSIONS: Bilateral elevation of IL-6 protein and mRNA is not limited to DRG homonymous to the injured nerve, but also extended to DRG that are heteronymous to the injured nerve. The results for IL-6 suggest that the neuroinflammatory reaction of DRG to nerve injury is propagated alongside the neuroaxis from the lumbar to the remote cervical segments. This is probably related to conditioning of cervical DRG neurons to injury.
- MeSH
- ELISA MeSH
- funkční lateralita fyziologie MeSH
- fyzikální stimulace MeSH
- hybridizace in situ MeSH
- hyperalgezie metabolismus MeSH
- imunohistochemie MeSH
- interleukin-6 biosyntéza genetika MeSH
- krční obratle MeSH
- krysa rodu rattus MeSH
- lumbosakrální krajina MeSH
- měření bolesti MeSH
- messenger RNA biosyntéza genetika MeSH
- nemoci sedacího nervu metabolismus MeSH
- neuralgie metabolismus MeSH
- počítačové zpracování obrazu MeSH
- potkani Wistar MeSH
- receptory interleukinu-6 biosyntéza genetika MeSH
- spinální ganglia metabolismus MeSH
- stenóza MeSH
- úžinové syndromy metabolismus MeSH
- vysoká teplota diagnostické užití MeSH
- western blotting MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
There is a growing body of evidence that cytokines contribute to both induction and maintenance of neuropathic pain derived from changes in dorsal root ganglia (DRG), including the activity of the primary sensory neurons and their satellite glial cells (SGC). We used immunofluorescence and in situ hybridization methods to provide evidence that chronic constriction injury (CCI) of the sciatic nerve induces synthesis of interleukin-6 (IL-6) in SGC, elevation of IL-6 receptor (IL-6R) and activation of signal transducer and activator of transcription 3 (STAT3) signalling. Unilateral CCI of the rat sciatic nerve induced mechanoallodynia and thermal hyperalgesia in ipsilateral hind paws, but contralateral paws exhibited only temporal changes of sensitivity. We demonstrated that IL-6 mRNA and protein, which were expressed at very low levels in naïve DRG, were bilaterally increased not only in L4-L5 DRG neurons but also in SGC activated by unilateral CCI. Besides IL-6, substantial increase of IL-6R and pSTAT3 expression occurred in SGC following CCI, however, IL-6R associated protein, gp130 levels did not change. The results may suggest that unilateral CCI of the sciatic nerve induces bilateral activation of SGC in L4-L5 DRG to transduce IL-6 signalling during neuroinflammation.
- MeSH
- cytokinový receptor gp130 genetika metabolismus MeSH
- funkční lateralita MeSH
- interleukin-6 genetika metabolismus MeSH
- krysa rodu rattus MeSH
- měření bolesti MeSH
- messenger RNA metabolismus MeSH
- modely nemocí na zvířatech MeSH
- nemoci sedacího nervu patologie patofyziologie MeSH
- neuroglie metabolismus MeSH
- potkani Wistar MeSH
- receptory interleukinu-6 genetika metabolismus MeSH
- regulace genové exprese fyziologie MeSH
- signální transdukce fyziologie MeSH
- spinální ganglia patologie patofyziologie MeSH
- transkripční faktor STAT3 metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- dítě MeSH
- finanční podpora výzkumu jako téma MeSH
- geny fyziologie genetika MeSH
- hyperkineze etiologie genetika klasifikace MeSH
- lidé MeSH
- polymorfismus genetický genetika MeSH
- psychomotorické poruchy etiologie genetika klasifikace MeSH
- receptory dopaminové genetika klasifikace MeSH
- receptory interleukinu-6 genetika účinky léků MeSH
- výzkumný projekt MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- srovnávací studie MeSH
