TNF-α In Lesions Research Articles

Pro-inflammatory activation following demyelination is required for myelin clearance and oligodendrogenesis.

Remyelination requires innate immune system function, but how exactly microglia and macrophages clear myelin debris after injury and tailor a specific regenerative response is unclear. Here, we asked whether pro-inflammatory microglial/macrophage activation is required for this process. We established a novel toxin-based spinal cord model of de- and remyelination in zebrafish and showed that pro-inflammatory NF-κB-dependent activation in phagocytes occurs rapidly after myelin injury. We found that the pro-inflammatory response depends on myeloid differentiation primary response 88 (MyD88). MyD88-deficient mice and zebrafish were not only impaired in the degradation of myelin debris, but also in initiating the generation of new oligodendrocytes for myelin repair. We identified reduced generation of TNF-α in lesions of MyD88-deficient animals, a pro-inflammatory molecule that was able to induce the generation of new premyelinating oligodendrocytes. Our study shows that pro-inflammatory phagocytic signaling is required for myelin debris degradation, for inflammation resolution, and for initiating the generation of new oligodendrocytes.

Influence of vitamin D deficiency on T cell subsets and related indices during spinal tuberculosis.

The present study investigated the effects of vitamin D deficiency on T cell subsets in patients with spinal tuberculosis. In addition, the influence of vitamin D deficiency was investigated on the expression of cytokines IL-1β, IL-6 and TNF-α in intervertebral disc lesions of patients. One hundred and seventeen patients with spinal tuberculosis who received operative treatment in the Department of Orthopedics in Wuhan City Third Hospital from March 2012 to March 2015 were collected. The patients were divided depending upon vitamin D content into the control group (64 cases, vitamin D content <25 nmol/l) and experimental group (53 cases, vitamin D content >50 nmol/l). Immunofluorescence method was applied to determine the content of T cell subsets in both groups of patients. Intervertebral disc lesion tissues of two groups of patients were obtained during surgery then treated with HE staining and immunohistochemical staining. The values of average optical density obtained under light microscope were observed as the expression quantities of IL-1β, IL-6 and TNF-α, to explore the relationship between vitamin D and the expression of cytokines. When vitamin D is lacking, the expression of T lymphocyte subsets in patients with spinal tuberculosis significantly decreased. Compared with experimental group, the difference was statistically significant (P<0.05). Further, the expression of cytokines IL-1β, IL-6 and TNF-α in intervertebral disc lesion tissues of patients with spinal tuberculosis were significantly higher than those of patients with spinal tuberculosis whose vitamin D content was normal (P<0.05). In the control group, vitamin D content was negatively correlated with the expression of IL-1β, IL-6 and TNF-α. The expression of T lymphocyte subsets in patients with vitamin D deficiency was significantly reduced, and the immune function decreased. The expression of IL-1β, IL-6 and TNF-α in lesions were significantly higher than those of patients with normal vitamin D content. In addition, the lower the content of vitamin D was, the more active the expression of inflammatory factors were, which was not conducive to the recovery of tuberculosis lesions.

Tumor Necrosis Factor-α and Interferon-γ, but not HTLV-I Tax, are Likely Factors in the Epidermotropism of Cutaneous T-Cell Lymphoma via Induction of Interferon-Inducible Protein-10

We have previously shown that Interferon-Inducible Protein-10 (IP-10), a cytokine chemotactic for CD4-positive lymphocytes, is overexpressed by lesional epidermal keratinocytes and probably accounts for the epidermotropism of cutaneous T-cell lymphoma (CTCL). The tax gene of human T-lymphotropic virus-I (HTLV-I) immortalizes CD4-positive lymphocytes, induces IFN-γ, and has been detected in patients with classical CTCL who are seronegative for HTLV-I. TNF-α is synergistic with IFN-γ for the induction of IP-10. We therefore decided to define the presence of tax, IFN-γ, TNF-α, and IP-10 in lesions of 19 adults with classical CTCL who were seronegative for HTLV-I. Lesional mRNAs for actin, TNF-α, IFN-γ, and tax were detected by reverse-transcriptase polymerase chain reaction (RT-PCR) amplification. In addition IP-10, TNF-α, and IFN-γ were detected and localized with immunocytochemistry of frozen sections. In agreement with previous observations IP-10 was overexpressed in lesional keratinocytes of all 19 patients. By RT-PCR, mRNA for IFN-γ was detected in lesions of 8, and for TNF-α in lesions of 13 patients. By immunocytochemistry, TNF-α was expressed by lesional keratinocytes in 10 of 13 tested patients, whereas IFN-γ was focally expressed by lesional lymphocytes and faintly by lesional keratinocytes in 9 of 13 tested patients, tax mRNA was not detected in lesions of any patient, but was easily detectable in cutaneous lesions or peripheral blood of control patients who were seropositive for HTLV-I. We conclude that TNF-α and IFN-γ may cause epidermotropism by inducing IP-10. However, the tax gene of HTLV-I does not appear to be involved in the pathogenesis of classical CTCL.