Hemokinin 1 mouse

OBJECTIVE: Hemokinin-1, the newest tachykinin encoded by the preprotachykinin C (Tac4) gene, is predominatly produced by immune cells. Similarly to substance P, it has the greatest affinity to the tachykinin NK1 receptor, but has different binding site and signaling mechanisms. Furthermore, several recent data indicate the existence of a not yet identified own receptor and divergent non-NK1-mediated actions. Since there is no information on its functions in the airways, we investigated its role in endotoxin-induced pulmonary inflammation.

BACKGROUND: Efficient development of atopic diseases requires interactions between allergen and adjuvant to initiate and amplify the underlying inflammatory responses. Substance P (SP) and hemokinin-1 (HK-1) are neuropeptides that signal through the neurokinin-1 receptor (NK1R) to promote inflammation. Mast cells initiate the symptoms and tissue effects of atopic disorders, secreting TNF and IL-6 after FcεRI cross-linking by antigen-IgE complexes (FcεRI-activated mast cells [FcεRI-MCs]). Additionally, MCs express the NK1R, suggesting an adjuvant role for NK1R agonists in FcεRI-MC-mediated pathologies; however, in-depth research addressing this relevant aspect of MC biology is lacking.

The protective immunization rates in response to hepatitis B vaccination in chronic kidney disease (CKD) patients are lower than response rates in the general population because of genetic and CKD-related factors as well as logistic problems with a proper providing of the recommended vaccination schedules. This review focuses on third-generation vaccines and adjuvanted vaccines commercially introduced in some countries, investigated in clinical trials, especially involving CKD patients or used only in the experimental studies. In order to improve the immunization rate, the use of third-generation vaccines (yeast-derived pre-S2/S HBV vaccines, mammalian cell-derived pre-S2/S HBV vaccines, mammalian cell-derived pre-S1/pre-S2/S HBV vaccines), novel adjuvants (AS04, AS02, phosphorothioate oligodeoxyribonucleotide, hemokinin-1, a polysaccharide based on delta inulin, nano-complex Hep-c, cyclic diguanylate) or immunostimulants for enhancement of immunogenicity of existing recombinant hepatitis B vaccines is tried to improve results of hepatitis B vaccination prior to dialysis commencement or already on renal replacement therapy.

The most recently identified tachykinin, hemokinin-1, was cloned from mouse bone marrow. While several studies indicated that hemokinin-1 is involved in pain and inflammation, the physiological functions of hemokinin-1 are not fully understood. Our previous research demonstrated that the intrathecal (i.t.) administration of hemokinin-1 (0.00625-1.6nmol) dose-dependently induced nociceptive behaviors, consisting of scratching, biting and licking in mice, which are very similar with the nociceptive behaviors induced by the i.t. administration of substance P. Low-dose (0.0125nmol) hemokinin-1-induced nociceptive behavior was inhibited by a specific NK1 receptor antagonist; however, high-dose (0.1nmol) hemokinin-1-induced nociceptive behavior was not affected. In the present study, we found that the nociceptive behaviors induced by hemokinin-1 (0.1 nmol) were inhibited by the i.t. co-administration of MK-801 or D-APV, which are NMDA receptor antagonists.