Tumor associated neutrophils (TANs) are frequently detected in triple-negative breast cancer (TNBC). Recent studies also reveal the importance of promoting tumor progression and metastasis during cancer. However, mechanisms regulating neutrophil trafficking to tumors less clear. We sought determine whether is determined directly by malignant potential cells. found that conditioned media (TCM) harvested from highly aggressive, metastatic TNBC cells induced a polarized morphology robust...

The selective use by Toll-like receptor 4 of an adaptor protein may aid in the development safer vaccine adjuvants.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease characterized by collagen deposition within the lung interstitium. Bacterial infection associated with increased morbidity more rapid mortality in IPF patient populations, pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) are commonly isolated from lungs of hospitalized patients IPF. Despite this, effects fibrotic injury on critical immune responses to remain unknown. In present study, we show that,...

Abstract Pseudomonas aeruginosa (PA) infection in cystic fibrosis (CF) lung disease causes airway neutrophilia and hyperinflammation without effective bacterial clearance. We evaluated the immunostimulatory activities of lipid A, membrane anchor LPS, isolated from mutants PA that synthesize structural variants, present airways patients with CF, to determine if they correlate severity progression. In a subset severe late stage CF disease, unique hepta-acylated hepta-1855, is synthesized....

Tumor-associated neutrophils are found in many types of cancer and often reported to contribute negative outcomes. The presence transforming growth factor-beta (TGF-β) the tumor microenvironment reportedly contributes skewing a more pro-tumor phenotype. effects TGF-β on neutrophil signaling migration are, however, unclear. We sought characterize both primary human neutrophil-like cell line HL-60 determine whether it directly induces migration. that TGF-β1 does not induce chemotaxis transwell...

G protein–coupled receptors (GPCRs) that couple to the Gα i family of proteins are key regulators cell and tissue physiology. Our previous work has revealed new roles for in regulating migration neutrophils fibrosarcoma cells downstream activated chemoattractant receptors. Here, we used an intact proximity–based labeling coupled tandem mass tag (TMT)–based quantitative proteomics analysis identify selectively interacted with GTP-bound form i1 . Multiple targets were identified validated a...

LPS delays neutrophil apoptosis by a process generally assumed to involve cell-intrinsic TLR4 signaling. However, survival responses have been reported be monocyte-dependent, which would indicate more complexity than is currently appreciated. We compared the of conventionally purified vs highly neutrophils confirm or refute need for secondary cell-types and identify cellular molecular mechanisms involved. Direct stimulation failed extend neutrophils, but activity was retained in less pure...

Tumor-associated neutrophils are found in many types of cancer and often reported to contribute negative outcomes. The presence transforming growth factor-beta (TGF-β) the tumor microenvironment reportedly contributes skewing a more pro-tumor phenotype. effects TGF-β on neutrophil signaling migration are, however, unclear. We sought characterize both primary human neutrophil-like cell line HL-60 determine whether it directly induces migration. that TGF-β1 does not induce chemotaxis transwell...

ABSTRACT Neutrophils have tumor-promoting roles in breast cancer and are detected higher numbers aggressive tumors. How tumors recruit neutrophils remains undefined. Here, we investigated the of TGF-β1 TNF-α regulation neutrophil recruitment by cells. pro-inflammatory factors upregulated induce epithelial to mesenchymal transitions (EMT), a process linked cell aggressiveness. We report that, as expected, dual treatment with induces EMT signatures premalignant M2 cells, which part MCF10A...

Abstract G protein-coupled receptors (GPCRs) that couple to the Gi family of proteins are key regulators cell and tissue physiology. Our recent work has discovered novel roles for Gα i in migration neutrophils fibrosarcoma cells downstream activated chemoattractant receptors, but molecular target(s) these processes remain be identified. We adopted an intact proximity-based labeling approach using BioID2 coupled tandem mass tag (TMT)-based quantitative proteomics identify selectively interact...

Abstract Tumor associated neutrophils (TANs) are frequently detected in triple-negative breast cancer (TNBC). Recent studies also reveal the importance of promoting tumor progression and metastasis during cancer. However, mechanisms regulating neutrophil trafficking to tumors less clear. We sought determine whether is determined directly by malignant potential cells. found that conditioned media (TCM) harvested from highly aggressive, metastatic TNBC cells induced a polarized morphology...

Abstract Pseudomonas aeruginosa infection in cystic fibrosis (CF) lung disease causes airway neutrophilia and hyperinflammation without being cleared effectively. We evaluated the immunostimulatory activities of lipid A variants synthesized by P. (PA) exclusively CF patients to determine if they correlate with severity progression. One third PA isolates from late severe stage express a unique hepta–acylated A; hepta-1855 (m/z=1855) isoform. In primary cell cultures, we found that functioned...

Abstract We reported previously that the vaccine adjuvant monophosphoryl lipid A (MPLA) could behave as a TRIF-biased agonist of TLR4, with mostly intact TRIF-dependent outcomes but less MyD88/TRIF co-dependent activation proinflammatory cytokines, and proposed TRIF-bias was an important component MPL’s success clinically safe immunostimulant. Taking pharmacological approach, we have now found synthetic MPLA (sMLA) has approximately 10% potency Lipid (sLipid A) for all TRIF signaling tested,...

Abstract During tumor development, neutrophils and other immune cells infiltrate the niche. Neutrophils have been shown to primarily pro-tumorigenic effects, high levels of circulating are indicative a poor prognosis. Tumor-associated (TANs) migrate tumors by sensing chemical gradients produced cells; however, mechanisms which TANs interact impact each remain be determined. It has that malignant breast tumors, such as triple-negative harbor more compared less aggressive tumors. We...

Cell-migration and adhesion are fundamental biological processes regulated by chemokine G-protein-coupled receptors that couple to PTX-sensitive Gi proteins. The role of Gβγ subunits released from in signaling has been well characterized. In contrast, Gαi thought have no direct function. Our laboratory recently uncovered a for Gαi-GTP regulating cell adhesion. However, effector responsible was not identified. To discover novel targets active Gαi, we used BioID2 proximity-based labeling...