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BackgroundsCXC chemokine ligand 16 (CXCL16) is a soluble chemokine with a transmembrane domain, playing an important role in inflammatory regulation. NF-κB has a critical role in tumor progression. Recent studies focused on the effect of CXCL16 on tumor progression. However, few reports showed the influence of CXCL16 on lung cancer, especially in regulating NF-κB activity. Here we investigated CXCL16 expression and its clinical significance in lung cancer, as well as the effect on lung cancer cell biological characteristics by regulating NF-κB.Material/MethodsCXCL16 expression in lung cancer was detected and its associations with clinical characteristics were analyzed. Proliferation and invasion of A549 and PC-9 cells was measured before and after silencing CXCL16 or inhibiting the NF-κB pathway, separately.ResultThe positive rate of CXCL16 in lung cancer tissue was significantly higher than that in adjacent tissue, and that in patients with lymphatic metastasis was significantly higher than that in patients without (all, P<0.05). The positive rate of CXCL16 was significantly (P<0.05) positively corrected with poor prognosis of lung cancer. Silencing CXCL16 not only suppressed proliferation and invasion of A549 and PC-9 cells, but also significantly (P<0.05) inhibited c-Rel, p105, and Rel-B in the NF-κB pathway. Inhibiting NF-κB also suppressed proliferation and invasion of A549 and PC-9 cells, which was similar to the results after silencing CXCL16.ConclusionsEnhanced CXCL16 expression in lung cancer tissue promoted the proliferation and invasion of lung cancer cells. CXCL16 might promote proliferation and invasion of lung cancer by regulating the NF-κB pathway.

Tumor necrosis factor (TNF) is a proinflammatory cytokine, which is involved in physiological and pathological processes and has been found to be crucial for pain development. In the current study, we were interested in the effects of blocking Tumor necrosis factor receptor 1 (TNFR1) signaling on neuropathic pain after peripheral nerve injury with the use of transgenic mice and pharmacological inhibition. We have previously shown that TNFR1−/− mice failed to develop neuropathic pain and depressive symptoms after chronic constriction injury (CCI). To investigate the therapeutic effects of inhibiting TNFR1 signaling after injury, we delivered a drug that inactivates soluble TNF (XPro1595). Inhibition of solTNF signaling resulted in an accelerated recovery from neuropathic pain in males, but not in females. To begin exploring a mechanism, we investigated changes in N-methyl-D-aspartate (NMDA) receptors because neuropathic pain has been shown to invoke an increase in glutamatergic signaling. In male mice, XPro1595 treatment reduces elevated NMDA receptor levels in the brain after injury, whereas in female mice, NMDA receptor levels decrease after CCI. We further show that estrogen inhibits the therapeutic response of XPro1595 in females. Our results suggest that TNFR1 signaling plays an essential role in pain induction after CCI in males but not in females.