Inflammation

Transient receptor potential A1 (TRPA1) is an ion channel found on the plasma membrane of many cell types that functions in diverse sensory processes such as pain and temperature. The TRPA1 ion channel is specifically expressed in nociceptive neurons, as well as neurons who express the related protein TRPV1. In fact, Brierly et al used a TRPA1 antibody to discover that this ion channel is largely present on smaller neurons vs larger ones (1).

Platelet endothelial cell adhesion molecule 1 (PECAM1), also known as cluster of differentiation 31 (CD31), is a cell-surface glycoprotein expressed on platelets, monocytes, neutrophils, some types of T-cells and NK (natural killer) cells. It makes up a large portion of the endothelial cell intercellular junctions. CD31/PECAM1 is a member of the immunoglobulin superfamily and plays many different roles involving leukocyte migration under most inflammatory conditions, angiogenesis, integrin activation, atherosclerosis and thrombopoiesis.

The protein TLR6 is one member of the large Toll-like receptor (TLR) family, which governs the activation of the innate immunity system and pathogen recognition in cells. The TLR family is highly conserved from Drosophila to humans, and all the family members have a high degree of both functional and structural homology. TLRs modulate cytokine production by cells that is required to effectively establish innate immunity.

RANKL is the ligand for the receptor activator of NFkB (RANK) that belongs to the tumor necrosis factor receptor (TNFR) superfamily. RANK overexpression induces the NFkB and c-Jun-terminal kinase (JNK) downstream pathways. This pathway has been studied in detail in the bone remodeling system with regards to osteoclast activity and induction.

NFkB-activating kinase (NAK) is serine/threonine protein kinase that is a member of the IkB kinase (IKK) family and plays a key role in cellular inflammatory responses to foreign stimuli and agents. Fitzgerald, et al.

IKK beta, also known as IKK2, activates the NFkB complex by phosphorylating the NFkB inhibitor, IkBa. Several transcript variants, some protein-coding and some not, have been found for IKKB. The Nuclear Factor-kappa B (NF-kB) family of transcription factors regulates the expression of a wide range of genes critical for immune and inflammatory responses, cell survival, immune development, and cell proliferation (1). NF-kB was firstly identified by Dr.

MMP2 is an extracellular matrix degradative peptidase enzyme that belongs to the large family of matrix metalloproteinases (MMPs) which each have different substrate specificities. Aberrant or derailed expression of various MMPs through loss of negative checks is strongly associated with tumor invasion, metastasis, and angiogenesis, as compared to tightly controlled physiological processes such as tissue remodeling, rebuilding, and embryonic development.

TREM1 is pro-inflammatory gene that stimulates neutrophil and monocyte-mediated inflammatory responses. This protein is highly expressed in adult liver, lung and spleen. It is also present in the lymph node, spinal cord and heart tissues. TREM-1 plays a critical role in acute inflammatory responses to bacteria. In organs such as the liver, damage occurring due to irritants such as alcohol causes TREM-1 to amplify the inflammatory response by mediating a signalling pathway.

TRPV1: Show Me Where it Hurts

TRPV1 (transient receptor potential cation channel subfamily vanilloid member type 1) is a polymodal nociceptor that is commonly expressed in peripheral nerve endings and dorsal root ganglia. It is activated by heat, low pH, vanilloids, capsaicin, and other noxious stimuli and is involved in the transmission and modulation of pain. Not surprisingly, TRPV1 is directly related to hyperalgesia—increased sensitivity to pain—as hyperalgesia is significantly reduced when TRPV1 is genetically eliminated or pharmacologically blocked.