LGD1069 (Targretin®) is a selective retinoid X receptor (RXR) ligand, which is used in patients for cutaneous T-cell lymphoma. Our published study reported that LGD1069 inhibited tumor-induced angiogenesis in non-small cell lung cancer. In present study, we found that LGD1069 suppressed the proliferation, adhesion, invasion and migration of endothelial cells directly, and affected the expression of vegf and some matrix genes.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3120806/
G protein βγ subunit-dependent signaling is important for chemoattractant-dependent leukocyte chemotaxis. Selective small molecule targeting of phosphoinositide 3-kinase (PI3-kinase) γ catalytic activity is a target of interest for anti-inflammatory pharmaceutical development. In this study, we examined whether small-molecule inhibition of Gβγ-dependent signaling, including Gβγ-dependent activation of PI3-kinase γ and Rac1, could inhibit chemoattractant-dependent neutrophil migration in vitro and inflammation in vivo. Small-molecule Gβγ inhibitors suppressed fMLP-stimulated Rac activation, superoxide production, and PI3-kinase activation in differentiated HL60 cells. These compounds also blocked fMLP-dependent chemotaxis in HL60 cells and primary human neutrophils. Systemic administration inhibited paw edema and neutrophil infiltration in a mouse carrageenan-induced paw edema model. Overall, the data demonstrate that targeting Gβγ-regulation may be an effective anti-inflammation strategy.
http://molpharm.aspetjournals.org/content/73/2/410.full
The human Ca21-activated chloride channel-2 (CLCA2) is expressed in
normal breast epithelium but not in breast tumors of different stages of
progression. Northern analysis of nontransformed and transformed
breast epithelial cell lines revealed CLCA2 expression in the nontransformed
cell line MCF10A and the nontumorigenic cell line MDA-MB-453,
whereas all tumorigenic cell lines were negative (MDA-MB-231, MDAMB-
435, MDA-MB-468, and MCF7). When stably reintroduced into
CLCA2-negative MDA-MB-231 and MDA-MB-435 cells, CLCA2 expression
reduced Matrigel invasion in vitro and inducibility of s.c. and metastatic
tumors of MDA-MB-231 cells in nude mice. Our results suggest that
CLCA2 may act as a tumor suppressor in breast cancer.
cancerres.aacrjournals.org/content/59/21/5488.full.pdf
The human Ca21-activated chloride channel-2 (CLCA2) is expressed in
normal breast epithelium but not in breast tumors of different stages of
progression. Northern analysis of nontransformed and transformed
breast epithelial cell lines revealed CLCA2 expression in the nontransformed
cell line MCF10A and the nontumorigenic cell line MDA-MB-453,
whereas all tumorigenic cell lines were negative (MDA-MB-231, MDAMB-
435, MDA-MB-468, and MCF7). When stably reintroduced into
CLCA2-negative MDA-MB-231 and MDA-MB-435 cells, CLCA2 expression
reduced Matrigel invasion in vitro and inducibility of s.c. and metastatic
tumors of MDA-MB-231 cells in nude mice. Our results suggest that
CLCA2 may act as a tumor suppressor in breast cancer.
cancerres.aacrjournals.org/content/59/21/5488.full.pdf
G protein βγ subunit-dependent signaling is important for chemoattractant-dependent leukocyte chemotaxis. Selective small molecule targeting of phosphoinositide 3-kinase (PI3-kinase) γ catalytic activity is a target of interest for anti-inflammatory pharmaceutical development. In this study, we examined whether small-molecule inhibition of Gβγ-dependent signaling, including Gβγ-dependent activation of PI3-kinase γ and Rac1, could inhibit chemoattractant-dependent neutrophil migration in vitro and inflammation in vivo. Small-molecule Gβγ inhibitors suppressed fMLP-stimulated Rac activation, superoxide production, and PI3-kinase activation in differentiated HL60 cells. These compounds also blocked fMLP-dependent chemotaxis in HL60 cells and primary human neutrophils. Systemic administration inhibited paw edema and neutrophil infiltration in a mouse carrageenan-induced paw edema model. Overall, the data demonstrate that targeting Gβγ-regulation may be an effective anti-inflammation strategy.
http://molpharm.aspetjournals.org/content/73/2/410.full
Several chemoattractants have been measured in exhaled breath condensate (EBC) from
patients with COPD. The aim of this study was to compare the eosinophil and neutrophil chemotactic activity contained in EBC from healthy subjects and patients with COPD.
Methods: EBC collected using a commercially available condenser (EcoScreen; Erich Jaeger Viasys; Hoechberg, Germany) was compared in 45 COPD patients and 65 healthy subjects. EBC chemotactic activity for eosinophils and neutrophils was assessed using microchambers (Boyden; Neuro Probe; Gaithersburg, MD). Chemotactic index (CI) was used to evaluate cell migration.
Results: EBC from patients with COPD (CI, 2.210.16 [meanSEM]) and healthy subjects (CI, 1.670.11) displayed significant neutrophil chemotactic activity (p<0.0001 for both), which was however higher in patients with COPD (p<0.001). Healthy smokers had a significantly raised CI for neutrophils by comparison with healthy nonsmokers (p<0.01) and ex-smokers (p<0.05). Likewise, current COPD smokers tended to have greater neutrophil CI than COPD who stopped smoking (p0.08). COPD ex-smokers had raised chemotactic activity by comparison with healthy ex-smokers (p<0.05). Anti–interleukin-8 (106 g/mL) antibodies reduced neutrophil chemotactic activity by 35.2% (p<0.05). EBC also contained significant eosinophil chemotactic activity in healthy subjects (CI, 1.680.09; p<0.0001) and patients with COPD (CI, 1.230.07; p<0.01), with a significantly lower CI in patients with COPD as compared to healthy subjects (p<0.001). Smoking did not influence eosinophil
chemotactic activity in healthy subjects or patients with COPD.
http://chestjournal.chestpubs.org/content/131/6/1672.full.html
PURPOSE. The purpose of this study was to examine expression of platelet-derived growth factor (PDGF) and PDGF receptors in the human cornea and to study the effects of the PDGF isotypes on proliferation and chemotaxis of human corneal fibroblasts. The effects of interleukin (IL)-lai, bone morphogenic protein (BMP)2, and BMP4 on chemotaxis of human corneal fibroblasts were also studied.
www.iovs.org/content/40/7/1364.full.pdf
ABSTRACT: Pulmonary alveolar proteinosis (PAP) is a rare disease of unknown
aetiology characterized by accumulations of lipoproteinaceous material within the
alveoli. The alveolar macrophages become increasingly foamy, and are thought to
have a role in the pathogenesis of PAP. However, the mechanisms of macrophage
recruitment are unclear.
In the bronchoalveolar lavage fluid (BALF) of four patients with PAP and 20
normal control subjects, the following were examined: the monocyte chemotactic
activity due to the chemokine monocyte chemoattractant protein (MCP)-1 with the
use of a chemotactic chamber assay, the levels of MCP-1 by enzyme-linked immunosorbent
assay, and the MCP-1 expression on lavage cells by immunocytochemistry
and in situ hybridization.
The monocyte chemotactic activity in the BALF of the PAP patients was markedly
elevated, and the activity was completely absorbed by treatment with anti-MCP-1.
The MCP-1 levels in the BALF were surprisingly high in the PAP group (25,100472
pg.mL-1), whereas low levels of MCP-1 were detected in the normal control subjects
(mean: never smokers 4.8; smokers 10.4 pg.mL-1). MCP-1 protein and messenger
ribonucleic acid were expressed by macrophages from the PAP patients, and the
expression was reduced according to foaming of the cells; there were monocyte-like
macrophages with strong expression, small foamy cells with moderate expression,
large foamy cells with a faint expression of MCP-1, and ghost cells with no expression.
However, the increase of macrophage number in the PAP BALF was relatively small.
These data suggest that monocyte chemoattractant protein-1 expression by alveolar
macrophages represents an amplification mechanism for the recruitment of additional
macrophages to the alveoli in pulmonary alveolar proteinosis. It is possible that an
ingestion of an excess of alveolar materials in pulmonary alveolar proteinosis may
impair the macrophage function and the survival, resulting in the lack of a prominent
increase in the macrophage number in bronchoalveolar lavage fluid.
www.ersj.org.uk/content/14/2/383.full.pdf
