- Title Information
- Title
- Differential Effects of Proinflammatory Cytokines on TGF-β1-Mediated Biomechanical and Biochemical Properties of 3D Human Fibroblast Tissues
- Type of Resource (primo)
- dissertations
- Name:
Personal
- Name Part
- St. Angelo, Katerina
- Role
- Role Term:
Text
- creator
- Name:
Personal
- Name Part
- Morgan, Jeffrey
- Role
- Role Term:
Text
- Advisor
- Name:
Personal
- Name Part
- Horrigan, Diana
- Role
- Role Term:
Text
- Reader
- Name:
Personal
- Name Part
- Y. Schell,, Jacquelyn
- Role
- Role Term:
Text
- Reader
- Name:
Corporate
- Name Part
- Brown University. Biology and Medicine: Biotechnology
- Role
- Role Term:
Text
- sponsor
- Origin Information
- Copyright Date
- 2026
- Physical Description
- Extent
- 10, 47 p.
- digitalOrigin
- born digital
- Note:
thesis
- Thesis (Sc. M.)--Brown University, 2026
- Genre (aat)
- theses
- Abstract
- Fibrosis is driven by excessive extracellular matrix (ECM) deposition and is a hallmark of chronic diseases including pulmonary fibrosis, liver cirrhosis, and cardiac fibrosis. TGF-β1 is the primary driver of fibroblast activation, promoting myofibroblast differentiation, collagen synthesis, and increased tissue stiffness. However, the fibrotic environment contains a diverse array of proinflammatory cytokines that may modulate TGF-β1’s effects on fibroblasts. To investigate this, we used a scaffold-free 3D in vitro ring tissue model in which human fibroblasts self-assemble into a collagen-rich connective tissue over 14 days. Ring tissues were treated with TNF-α, IL-18, IL-1β, IFN-γ, or IL-1α, alone and in combination with TGF-β1. Tissue size, total DNA, total collagen, biomechanical properties (ultimate tensile strength and maximum tangent modulus), and histology were assessed at days 7 and 14. TGF-β1 increased collagen accumulation and the strength and stiffness of ring tissues. TNF-α, IL-1β, and IL-1α each reduced tissue size, total collagen, and the tensile strength and stiffness of both control and TGF-β1-stimulated tissues, effectively counteracting TGF-β1-mediated collagen accumulation. Histological analysis revealed that TNF-α and IL-1β disrupted collagen fiber architecture and increased nuclear pyknosis, effects that were most pronounced in TGF-β1-stimulated tissues. In contrast, IL-18 and IFN-γ had little to no effect on collagen accumulation or tissue mechanics in either control or TGF-β1-stimulated tissues. These findings demonstrate that proinflammatory cytokines have divergent effects on fibroblast-mediated collagen deposition: TNF-α, IL-1β, and IL-1α act as counter regulators of TGF-β1-driven fibrosis, while IL-18 and IFN-γ are largely neutral in this context. This work highlights the complexity of cytokine crosstalk in fibrosis and demonstrates the utility of 3D in vitro tissue models for dissecting cytokine-specific contributions to collagen accumulation and tissue biomechanics.
- Subject
- Topic
- microtissue
- Subject
- Topic
- Fibrosis
- Subject
- Topic
- 3D Cell Culture
- Subject
- Topic
- 3D cel ring model
- Language
- Language Term (ISO639-2B)
- English
- Record Information
- Record Content Source (marcorg)
- RPB
- Record Creation Date
(encoding="iso8601")
- 20260427