A non-peptide substance P antagonist (CP-96,345) inhibits morphine-induced NF-kappa B promoter activation in human NT2-N neurons.

Opioids and the neuropeptide substance P (SP) modulate the expression of inflammatory cytokines and chemokines, which are under the control of nuclear factor kappaB (NF-kappaB). We investigated whether the neurokinin-1 receptor (SP receptor) pathway is biologically involved in morphine-mediated modulation of NF-kappaB promoter activation in a human neuronal cell line (NT2-N) that expresses both the mu-opioid receptor (MOR) and the SP receptor. Morphine significantly enhanced NF-kappaB promoter-directed luciferase activity in NT2-N neurons.

Interleukin-1beta stimulates macrophage inflammatory protein-1alpha and -1beta expression in human neuronal cells (NT2-N).

Chemokines are important mediators in immune responses and inflammatory processes of neuroimmunologic and infectious diseases. Although chemokines are expressed predominantly by cells of the immune system, neurons also express chemokines and chemokine receptors. We report herein that human neuronal cells (NT2-N) produce macrophage inflammatory protein-1alpha and -1beta (MIP-1alpha and MIP-1beta), which could be enhanced by interleukin (IL)-1beta at both mRNA and protein levels.

Human neuronal cells (NT2-N) express functional substance P and neurokinin-1 receptor coupled to MIP-1 beta expression.

Substance P (SP), the most extensively studied and potent member of the tachykinin family, is a major modulator of inflammation and immunomodulatory activities within the central and peripheral nervous systems. We have examined the gene expression of SP and its receptor in a human neuronal cell line (NT2-N). Using reverse transcribed polymerase chain reaction (RT-PCR), the four isoforms of preprotachykinin-A gene transcripts (alpha, beta, gamma, and delta) were detected in the NT2-N.