The TrkB gene encodes a high-affinity neurotrophin receptor, which is involved in the differentiation and function of neuronal cells. Additionally, TrkB has been associated with chronic inflammatory disease, i.e. ulcerative colitis and bronchial asthma. Patients suffering from allergic asthma feature elevated neurotrophin levels in the peripheral blood as well as in lung tissue, and neurotrophin release was increased upon exposure of inflammatory cells to allergic stimuli. Hence, the purpose of this study was to investigate the possible role and the regulation of the TrkB neurotrophin receptor during inflammation.

Compared to administration of phosphate buffered solution (PBS), intraperitoneal injection of lipopolysaccharide (LPS, Escherichia coli, serotype 0111:B4; 10 mg/kg) into otherwise healthy male C57/Bl6 mice increased TrkB mRNA levels more than 3-fold in the lungs, but in no other organs examined (n=4 per group). Likewise, TrkB protein in the lungs increased gradually between 6 hrs and 24 hrs after LPS injection. The inflammatory reaction in LPS-treated mice was assessed by their elevated levels of IL-1, IL-6 and TNFa.

TrkB mRNA was also significantly upregulated in pulmonary epithelial cells (Calu-6) that had been incubated for 6 hrs with TNFa (25 ng/ml). In contrast, TNFa had no effect on TrkB expression in monocytic cell lines. These findings indicate that TrkB expression in the lungs and in pulmonary epithelial cells are stimulated by pro-inflammatory signals. Bioinformatic analysis revealed that the human TrkB promoter contains at least 4 highly preserved binding sites for NF-kB, which is a major transcriptional regulator during inflammation. Thus, it remains to be explored whether increased expression of TrkB during pulmonary inflammation is due to NF-kB activation or mediated through other, yet unknown pathways.