CDB25:0003738 HP — TLR4

Experimentally validated in Human; Orthology-inferred in Mouse, Rat, Frog, Zebrafish, Macaque, Pig, Dog, Cow, Horse, Marmoset, Sheep

Title

Journal:; Year Published:

Abstract

Haptoglobin Acts as a TLR4 Ligand to Suppress Osteoclastogenesis via the TLR4-IFN-β Axis.

Journal of immunology, 2019; PubMed, Homo sapiens HP — Homo sapiens TLR4

ABSTRACT: Haptoglobin (Hp), a type of acute-phase protein, is known to have a systemic anti-inflammatory function and to modulate inflammation by directly affecting immune cells, such as T cells, dendritic cells, and macrophages. However, the effects of Hp on osteoclast differentiation are not well studied, even though osteoclast precursor cells belong to a macrophage-monocyte lineage. In this study, we found that the bone volume was reduced, and the number of osteoclasts was increased in Hp-deficient mice compared with wild-type mice. Moreover, our in vitro studies showed that Hp inhibits osteoclastogenesis by reducing the protein level of c-Fos at the early phase of osteoclast differentiation. We revealed that Hp-induced suppression of c-Fos was mediated by increased IFN-β levels. Furthermore, Hp stimulated IFN-β via a TLR4-dependent mechanism. These results demonstrate that Hp plays a protective role against excessive osteoclastogenesis via the Hp-TLR4-IFN-β axis.

Basic Information on HP

Ligand Name: haptoglobin

Other Symbols: N/A

Ligand Location: secreted based on hpa, perplexity, uniprot

HGNC Gene Symbol Report: HP

GeneCards: HP

HGNC Gene Group: Sushi domain containing

Functional Annotations for HP

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Receptors for HP

HP — ITGAM ・ HP — ITGB2 ・ HP — CD163 ・ HP — CD22

Basic Information on TLR4

Receptor Name: toll like receptor 4

Other Symbols: hToll, CD284, TLR-4, ARMD10

Receptor Location: cell membrane based on hpa, perplexity, uniprot

HGNC Gene Symbol Report: TLR4

GeneCards: TLR4

HGNC Gene Group: TIR domain containing, CD molecules

Functional Annotations for TLR4

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Ligands for TLR4

BGN — TLR4 ・ DEFB4A — TLR4 ・ HSP90B1 — TLR4 ・ HSPA1A — TLR4 ・ S100A8 — TLR4 ・ S100A9 — TLR4 ・ SFTPD — TLR4 ・ ZG16B — TLR4 ・ DCN — TLR4 ・ FGA — TLR4 ・ FGB — TLR4 ・ FGG — TLR4 ・ PRG4 — TLR4 ・ AHSG — TLR4 ・ ANXA2 — TLR4 ・ CCN1 — TLR4 ・ CIRBP — TLR4 ・ CXCL10 — TLR4 ・ FCN2 — TLR4 ・ HMGB1 — TLR4 ・ HSPA4 — TLR4 ・ LGALS9 — TLR4 ・ MMP9 — TLR4 ・ NAMPT — TLR4 ・ RBP4 — TLR4 ・ RETN — TLR4 ・ S100A1 — TLR4 ・ S100A12 — TLR4 ・ S100A4 — TLR4 ・ SAA1 — TLR4 ・ SFTPA1 — TLR4 ・ TNC — TLR4 ・ WNT5A — TLR4