Tumor necrosis factor-α (TNF-α) is a proalgesic cytokine that is commonly expressed following tissue injury. TNF-α expression not only promotes inflammation but can also lead to pain hypersensitivity in nociceptors. With the established link between TNF-α and inflammatory pain, we identified its increased expression in the teeth of patients affected with caries and pulpitis. We generated a transgenic mouse model (TNF-α glo ) that could be used to conditionally overexpress TNF-α. These mice were bred with a dentin matrix protein 1 (DMP1)-Cre line for overexpression of TNF-α in both the tooth pulp and bone to study oral pain that would result from subsequent development of pulpitis and bone loss. The resulting DMP1/TNF-α glo mice show inflammation in the tooth pulp that resembles pulpitis while also displaying periodontal bone loss. Inflammatory infiltrates and enlarged blood vessels were observed in the tooth pulp. Pulpitis and osteitis affected the nociceptive neurons innervating the orofacial region by causing increased expression of inflammatory cytokines within the trigeminal ganglia. With this new mouse model morphologically mimicking pulpitis and osteitis, we tested it for signs of oral pain with an oral function assay (dolognawmeter). This assay/device records the time required by a mouse to complete a discrete gnawing task. The duration of gnawing required by the DMP1/TNF-α glo mice to complete the task was greater than that for the controls; extended gnaw time in a dolognawmeter indicates reduced orofacial function. With the DMP1/TNF-α glo mice, we have shown that TNF-α expression alone can produce inflammation similar to pulpitis and osteitis and that this mouse model can be used to study dental inflammatory pain.
Tumour necrosis factor-a-induced protein-8 like-2 (TIPE2) is a newly identified immune negative regulator. The abnormal expression of TIPE2 has been found in several human inflammatory diseases. However, the expression level and clinical significance of TIPE2 in childhood asthma remain unclear. In this study, we detected TIPE2 expression in peripheral blood mononuclear cells (PBMC) from 42 children with asthma and 39 healthy controls by RT-PCR, qRT-PCR and Western blot. We also detected the levels of serum total immunoglobulin E (IgE), eosinophil (EO), interleukin-4 (IL-4) and interferon-c (IFN-c) and analysed the correlations of TIPE2 expression with IgE, EO, IL-4 and IFN-c. The results showed that TIPE2 mRNA and protein expression were decreased in children with asthma compared with healthy controls. The levels of IgE, EO and IL-4 in the children with asthma were obviously higher than those in normal controls, while the level of IFN-c in patients with asthma was significantly lower than that in healthy subjects. Furthermore, the expression level of TIPE2 mRNA was negatively correlated with IgE, EO and IL-4. However, no statistically significant correlation was found between TIPE2 mRNA expression and serum IFN-c level. In conclusion, our data suggest that reduced TIPE2 expression may contribute to the pathogenesis of childhood asthma.
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