Elastin‐derived peptide induces monocyte chemotaxis by increasing intracellular cyclic GMP level and activating cyclic GMP dependent protein kinase

Abstract

An elastin‐derived peptide with an average molecular mass of 25 kDa was shown to induce monocyte chemotaxis at the optimal concentration of 10‐1 μg/ml. Homologous deactivation test showed that monocytes exposed to the elastin‐derived peptide at 10‐1 μg/ml lost their chemotactic responsiveness when reexposed to the same stimulus. In conjunction with chemotactic response to the elastin‐derived peptide, intracellular guanosine 3′, 5′‐monophosphate (cGMP) levels were enhanced but intracellular adenosine 3′, 5′‐monophosphate (cAMP) levels were not. The monocyte migration induced by the elastin‐derived peptide was inhibited by cGMP dependent protein kinase (PKG) inhibitor, but not by cAMP dependent protein kinase inhibitor and protein kinase C inhibitor. These results suggest that the elastin‐derived peptide induces monocyte chemotaxis by increasing the level of cGMP, followed by activating PKG.

Targeted delivery of pentagalloyl glucose inhibits matrix metalloproteinase activity and preserves elastin in emphysematous lungs

“…The inability of adults to regenerate elastin has been attributed to the lack of perfect interplay between all the molecules participating in the process of elastin deposition [ 7 ]. Moreover, elastin degradation products (EDPs) act as chemoattractants for monocytes and further increase the inflammatory burden on the lungs [ 8 ]. Thus, protecting elastin from elastolytic damage and regenerating lost elastin would improve the mechanical function of damaged lungs.…”

Nanoparticle-based targeted delivery of pentagalloyl glucose reverses elastase-induced abdominal aortic aneurysm and restores aorta to the healthy state in mice

“…We have reported it before that PGG binds strongly to elastin and prevents its further degradation by elastases [12]. Such binding can avoid the generation of elastin peptides that are known chemoattractant to macrophages [34]. Thus, we hypothesize that PGG binding to elastin stops this inflammation, MMP secretion, and ECM degradation loop that exacerbate AAA progression.…”

Nanoparticle-based targeted delivery of pentagalloyl glucose reverses elastase-induced abdominal aortic aneurysm and restores aorta to the healthy state in mice

“…We showed it before that PGG binds strongly to elastin and prevents its further degradation 12 . Such binding can avoid generation of elastin peptides that are known chemoattractant to macrophages 33 .…”