What does TLR4 detect?
TLR4 has been long recognized as the sensing receptor for gram-negative lipopolysaccharide (LPS). In addition, it also binds endogenous molecules produced as a result of tissue injury. Hence, TLR4 represents a key receptor on which both infectious and noninfectious stimuli converge to induce a proinflammatory response.
Where are TLR4 found?
Tocris Summary for TLR4 Gene TLRs generally exist as homodimers (heterodimers have been reported) and are found on immune cells; macrophages, B lymphocytes and mast cells.
What cells have TLR4?
Besides being found in antigen-presenting cells, several TLRs, and more specifically, TLR4, have been identified in other cell types, such as endothelial cells [13, 14], myocytes [15], thyroid cells [16], endometrial cells [17], mesangial cells [18], and adipocytes [19].
What immune cells have TLR4?
In the human central nervous system (CNS), TLR4 is expressed by two types of non-neuronal supportive cells: the CNS residential macrophages or microglia and the macroglial cells such as astrocytes (65).
Do humans have TLR4?
The human TLR4 consists of an extracellular domain of 624 amino acids (residues 1–624), a transmembrane domain of 33 amino acids (residues 625–658), a proximal cytoplasmic domain of 159 amino acids (residues 659–818), and a distal cytoplasmic domain of 19 amino acids (residues 819–838).
What is the impact of TLR4 mutations on human health?
Recent reports have indicated that mutations in TLR4 may be associated with a higher incidence of gram-negative infections in intensive care unit patients exhibiting systemic inflammatory response syndrome or septic shock.
What cytokines are produced by TLR4?
Binding of LPS to TLR4 triggers signaling cascades (e.g., NFkB and MAPK) that culminate in the production of proinflammatory cytokines (TNFα, IL-1β, IL-6, IL-12) and type-I interferons required for propagation of the inflammatory response and ultimately pathogen destruction (3).
What is the impact of Tlr4 mutations on human health?
What Cytokines are produced by TLR4?
How is high IL-6 treated?
Currently, there are two available drugs based on human monoclonal antibodies against IL-6 receptor, tocilizumab (RoActemra, Roche) and sarilumab (Kevzara, Sanofi). IL-6 receptor inhibitors are currently licensed for several autoimmune disorders and are considered well tolerated and safe in general.