Epithelial Cxcl17 Does Not Affect Prostatic Foam Cell Inflammation but Promotes Immune Infiltration and May Suppress Basal Cell Proliferation
Poster #: 114
Session/Time: A
Author:
Samantha Jo McGuire, BS, MS
Mentor:
Petra Popovics, MS, PhD
Research Type: Basic Science
Abstract
INTRODUCTION:
Benign Prostatic Hyperplasia (BPH) is an age-related disease characterized by non-malignant prostate enlargement, leading to urethral constriction and lower urinary tract symptoms (LUTS). Prior work from our lab using a steroid hormone-induced mouse BPH model revealed macrophage infiltration into the prostatic lumen and foam cell formation. We identified the chemoattractant Cxcl17 as a potential mediator of macrophage migration. This study tested whether epithelial-derived Cxcl17 promotes macrophage recruitment and foam cell formation in a steroid hormone-induced mouse BPH model.
METHODS:
Cxcl17-knockout (KO) mice and wild-type (WT) littermates received subcutaneous testosterone and estradiol implants for 2, 6, or 12 weeks or underwent sham surgery. Urinary function was assessed via the Mouse Urovoid system. Prostates and the bladder were harvested and weighed. Immunohistochemistry assessed CD45 (immune cells), CD68 (macrophages), and Ki67 (proliferation) positivity; collagen and foam cells were visualized via picrosirius red and Oil Red O staining, respectively. Bulk RNA sequencing was performed on 2-week ventral prostates (VP).
RESULTS:
Cxcl17-KO T+E2 mice showed increased voiding frequency, while WT T+E2 mice had greater average void mass at week 4; other timepoints showed no significant differences. Cxcl17-loss did not affect prostate or bladder weight, nor bladder volume. Foam cell formation in the VP showed no genotype-specific changes. However, CD45/CD68+ immune cell infiltration was nearly abolished in Cxcl17-KO mice at 6 and 12 weeks. Collagen content and Ki67 expression were largely unchanged. RNA-seq revealed significant upregulation of basal cell markers (Krt5, Krt14, Trp63, Col4a2) in Cxcl17-KO T+E2 prostates.
CONCLUSION:
Our results demonstrate that Cxcl17 is dispensable for foam cell differentiation in the prostate, despite our initial hypothesis. In contrast, Cxcl17-loss abolished tissue macrophage numbers at the chronic stages of our model. Future studies will test whether Cxcl17 regulates basal cell proliferation or survival. Additionally, we are using laser capture microdissection to identify other epithelial cytokines that may drive foam cell formation in the prostate.
Benign Prostatic Hyperplasia (BPH) is an age-related disease characterized by non-malignant prostate enlargement, leading to urethral constriction and lower urinary tract symptoms (LUTS). Prior work from our lab using a steroid hormone-induced mouse BPH model revealed macrophage infiltration into the prostatic lumen and foam cell formation. We identified the chemoattractant Cxcl17 as a potential mediator of macrophage migration. This study tested whether epithelial-derived Cxcl17 promotes macrophage recruitment and foam cell formation in a steroid hormone-induced mouse BPH model.
METHODS:
Cxcl17-knockout (KO) mice and wild-type (WT) littermates received subcutaneous testosterone and estradiol implants for 2, 6, or 12 weeks or underwent sham surgery. Urinary function was assessed via the Mouse Urovoid system. Prostates and the bladder were harvested and weighed. Immunohistochemistry assessed CD45 (immune cells), CD68 (macrophages), and Ki67 (proliferation) positivity; collagen and foam cells were visualized via picrosirius red and Oil Red O staining, respectively. Bulk RNA sequencing was performed on 2-week ventral prostates (VP).
RESULTS:
Cxcl17-KO T+E2 mice showed increased voiding frequency, while WT T+E2 mice had greater average void mass at week 4; other timepoints showed no significant differences. Cxcl17-loss did not affect prostate or bladder weight, nor bladder volume. Foam cell formation in the VP showed no genotype-specific changes. However, CD45/CD68+ immune cell infiltration was nearly abolished in Cxcl17-KO mice at 6 and 12 weeks. Collagen content and Ki67 expression were largely unchanged. RNA-seq revealed significant upregulation of basal cell markers (Krt5, Krt14, Trp63, Col4a2) in Cxcl17-KO T+E2 prostates.
CONCLUSION:
Our results demonstrate that Cxcl17 is dispensable for foam cell differentiation in the prostate, despite our initial hypothesis. In contrast, Cxcl17-loss abolished tissue macrophage numbers at the chronic stages of our model. Future studies will test whether Cxcl17 regulates basal cell proliferation or survival. Additionally, we are using laser capture microdissection to identify other epithelial cytokines that may drive foam cell formation in the prostate.