Related Experiment Video

Updated: Jul 4, 2026

In Vitro Model of Human Cutaneous Hypertrophic Scarring using Macromolecular Crowding
08:20

In Vitro Model of Human Cutaneous Hypertrophic Scarring using Macromolecular Crowding

Published on: May 1, 2020

Histamine upregulates keratinocyte MMP-9 production via the histamine H1 receptor

Maria Gschwandtner1, Rahul Purwar, Miriam Wittmann

  • 1Department of Dermatology, Hannover Medical School, Hannover, Germany. gschwandtner.maria@mh-hannover.de

The Journal of Investigative Dermatology
|June 13, 2008
PubMed

Insights

Histamine stimulates skin cells to produce more matrix metalloproteinase 9 (MMP-9), a key enzyme in tissue remodeling. This increased MMP-9 enhances immune cell migration, potentially worsening allergic skin diseases.

Area of Science:

  • Dermatology
  • Immunology
  • Cell Biology

Background:

  • Skin inflammation and immune cell migration are central to allergic skin diseases.
  • Matrix metalloproteinase 9 (MMP-9) degrades basement membrane components, facilitating cell migration and tissue remodeling.

Purpose of the Study:

  • To investigate the expression of MMP-9 in human primary keratinocytes (KCs) stimulated by histamine.
  • To elucidate the role of histamine receptors in mediating MMP-9 production and subsequent immune cell migration.

Main Methods:

  • Enzyme-linked immunosorbent assay (ELISA) and zymography were used to quantify MMP-9 levels.
  • Immunohistological staining assessed type IV collagen degradation.
  • Co-culture systems of KCs and T cells evaluated T cell migration.

Main Results:

  • Histamine induced a dose-dependent upregulation of MMP-9 in cultured KCs and human skin biopsies.
  • The histamine H(1) receptor (H(1)R) mediated this effect, as shown by agonist and antagonist studies.
  • Histamine-induced MMP-9 led to type IV collagen destruction and increased T cell migration through an artificial basement membrane.

Conclusions:

  • Histamine stimulation enhances MMP-9 production in keratinocytes via the H(1)R.
  • This mechanism contributes to basement membrane degradation and increased immune cell migration.
  • Keratinocyte-derived MMP-9 represents a novel pathway in the pathogenesis of allergic skin diseases.

Related Concept Videos

Role of Matrix Metalloproteases in Degradation of ECM01:23

Role of Matrix Metalloproteases in Degradation of ECM

Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult body.
A...
Gastritis II: Pathophysiology01:26

Gastritis II: Pathophysiology

The pathophysiology of gastritis begins with the colonization of the stomach lining by Helicobacter pylori (H. pylori). This bacterium spreads mainly via the oral-oral route through saliva or shared utensils, and can also be transmitted in overcrowded or unhygienic environments through contaminated water, despite its brief survival outside the body.ColonizationOnce ingested, H. pylori enters the stomach and begins colonization by navigating through the mucus layer lining the stomach wall. It...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Chromatin Modification in iPS Cells01:32

Chromatin Modification in iPS Cells

Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...