PURPOSETo investigate the anti-adhesive mechanisms of PXL01 in sodium hyaluronate (HA) by using the rabbit lactoferrin peptide, rabPXL01 in HA, in a rabbit model of healing tendons and tendon sheaths. The mechanism of action for PXL01 in HA is interesting since a recent clinical study of the human lactoferrin peptide PXL01 in HA administered around repaired tendons in the hand showed improved digit mobility.MATERIALS AND METHODSOn days 1, 3, and 6 after tendon injury and surgical repair, reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) was used to assess mRNA expression levels for genes encoding the mucinous glycoprotein PRG4 (also called lubricin) and a subset of matrix proteins, cytokines, and growth factors involved in flexor tendon repair. RabPXL01 in HA was administered locally around the repaired tendons, and mRNA expression was compared with untreated repaired tendons and tendon sheaths.RESULTSWe observed, at all time points, increased expression of PRG4 mRNA in tendons treated with rabPXL01 in HA, but not in tendon sheaths. In addition, treatment with rabPXL01 in HA led to repression of the mRNA levels for the pro-inflammatory mediators interleukin (IL)-1β, IL-6, and IL-8 in tendon sheaths.CONCLUSIONSRabPXL01 in HA increased lubricin mRNA production while diminishing mRNA levels of inflammatory mediators, which in turn reduced the gliding resistance and inhibited the adhesion formation after flexor tendon repair.

2016-12-01·International Journal of Molecular Medicine3区 · 医学

Low concentrations of human neutrophil peptide ameliorate experimental murine colitis

3区 · 医学

Article

作者: Tanoue, Shiroh ; Hashimoto, Shinichi ; Uto, Hirofumi ; Sakiyama, Toshio ; Taguchi, Hiroki ; Tsubouchi, Hirohito ; Ibusuki, Kazunari ; Arima, Shiho ; Ido, Akio ; Nasu, Yuichiro ; Numata, Masatsugu ; Sasaki, Fumisato ; Komaki, Yuga ; Maeda, Takuro ; Kanmura, Shuji

Human neutrophil peptides (HNPs) not only have antimicrobial properties, but also exert multiple immunomodulatory effects depending on the concentration used. We have previously demonstrated that the intraperitoneal administration of high-dose HNP-1 (100 µg/day) aggravates murine dextran sulfate sodium (DSS)-induced colitis, suggesting a potential pro-inflammatory role for HNPs at high concentrations. However, the role of low physiological concentrations of HNPs in the intestinal tract remains largely unknown. The aim of this study was to examine the effects of low concentrations of HNPs on intestinal inflammation. We first examined the effects of the mild transgenic overexpression of HNP-1 in DSS-induced colitis. HNP-1 transgenic mice have plasma HNP-1 levels similar to the physiological concentrations in human plasma. Compared to wild-type mice treated with DSS, HNP-1 transgenic mice treated with DSS had significantly lower clinical and histological scores, and lower colonic mRNA levels of pro-inflammatory cytokines, including interleukin (IL)-1β and tumor necrosis factor (TNF)-α. We then injected low-dose HNP-1 (5 µg/day) or phosphate-buffered saline (PBS) intraperitoneally into C57BL/6N and BALB/c mice administered DSS. The HNP-1-treated mice exhibited significantly milder colitis with reduced expression levels of pro-inflammatory cytokines compared with the PBS-treated mice. Finally, we examined the in vitro effects of HNP-1 on the expression of cytokines associated with macrophage activation. Low physiological concentrations of HNP-1 did not significantly affect the expression levels of IL-1β, TNF-α, IL-6 or IL-10 in colonic lamina propria mononuclear cells activated with heat-killed Escherichia coli, suggesting that the anti-inflammatory effects of HNP-1 on murine colitis may not be exerted by direct action on intestinal macrophages. Collectively, our data demonstrated a biphasic dose-dependent effect of HNP-1 on DSS-induced colitis: an amelioration at low concentrations and an aggravation at high concentrations. Low concentrations of HNPs may contribute to the maintenance of intestinal homeostasis.

2011-12-01·Biomarkers4区 · 医学

Human neutrophil peptide in lung chronic allograft dysfunction

4区 · 医学

Article

作者: Trisha Becker ; Tereza Cervenka ; Chris H. Wendt ; Marshall I. Hertz ; Cavan Reilly

CONTEXTOur previous case-control study identified human neutrophil peptide (HNP) as a potential biomarker for bronchiolitis obliterans syndrome (BOS) in lung transplant recipients.OBJECTIVETo prospectively validate HNP as a biomarker for BOS.MATERIALS AND METHODSHNP was measured by ELISA in bronchoalveolar lavage (BAL) fluid in lung transplant recipients.RESULTSThe first HNP measurement after reaching baseline pulmonary function was predictive of developing BOS ≥2 (p = 0.0419). HNP remained elevated in those that developed BOS. The effect of potential confounders did not significantly impact BOS-free survival time.CONCLUSIONHNP levels are elevated early and persistently in those that develop BOS.

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